Virus World

Discover how Aedes aegypti mosquito eggs harboring ZIKV and CHIKV pose a new public health challenge, urging a revamp in control strategies. A groundbreaking discovery by scientists at the Federal University of Goiás (UFG) has unveiled that Aedes aegypti mosquito eggs can carry the ZIKV and CHIKV viruses, responsible for Zika and chikungunya respectively. This finding, highlighting a vertical transmission route, underscores a significant public health concern and calls for enhanced surveillance and control measures.

Unveiling the Mechanism of Vertical Transmission

The study, published in the source , marks a paradigm shift in understanding how these viruses are spread. Traditionally, transmission was thought to occur horizontally, with mosquitoes becoming vectors after biting an infected host. However, the detection of ZIKV and CHIKV in mosquito eggs before they hatch means mosquitoes can be born already infected, ready to spread the virus without prior contact with an infected host.

Implications for Public Health and Surveillance

Diego Michel Fernandes da Silva, the study's coordinator and a doctoral student at UFG, emphasized the significance of this discovery for public health. With mosquitoes capable of being born as carriers of these viruses, the potential for rapid spread increases, especially in urban environments. This adaptation mechanism allows for easier dispersal and poses a considerable challenge for controlling outbreaks of Zika and chikungunya. The study's findings necessitate a reconsideration of current prevention strategies, urging health authorities to intensify local epidemiological surveillance and explore innovative ways to eliminate the mosquito population.

Research Methodology and Findings

The research team captured Aedes aegypti eggs and adult mosquitoes across three major regions of Goiânia, Goiás, from January to September 2022. After isolating the heads and thoraxes of 1,570 adult females for analysis, the eggs were raised in laboratory conditions until they hatched. Among these, two groups tested positive for CHIKV and one for ZIKV, confirming that vertical transmission had occurred and that these mosquitoes could transmit the viruses upon reaching maturity. This revelation has profound implications for the fight against diseases like Zika and chikungunya. By demonstrating that viruses can be transmitted vertically from mosquitoes to their offspring, the study not only expands our understanding of these diseases' epidemiology but also underscores the urgent need for innovative control measures. As we grapple with the potential for increased transmission, this research serves as a critical call to action for health authorities worldwide to reassess and fortify their disease prevention strategies.

Cites Study Published in Revista da Sociedade Brasileira de Medicina Tropical (2024):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10890825/ 

The Zika virus could shrink tumors in a childhood cancer that makes up one in seven cancer deaths, a study from researchers at Nemours Children's Health in Florida suggests. Scientists are hoping to turn a deadly African virus into a therapy for a deadly childhood cancer. The Zika virus is a mosquito-borne infection that reduces levels of a protein which forms in excess levels in patients with certain cancers. A team of researchers in Florida has shown that, in mice at least, it can can wipe out  tumors known as neuroblastomas, which make up one in seven childhood cancer deaths and form in the nerve cells as children develop.

Scientists sent mice on scented chases and swabbed the armpits of people infected with dengue to pinpoint an odor that attracts mosquitoes. Being bit by a mosquito carrying dengue or Zika virus can make you sick. The infection can also make you even more attractive for other mosquitoes, new research finds. It’s an itchy concern for anyone infected, but also poses a major risk to communities at large: Mosquitoes that aren’t already carrying the viruses could be more drawn to sick humans, become infected, and go on to infect more humans. The spread of dengue, in particular, is a threat, with about half the world’s population at risk and hundreds of millions of cases each year. Most cases are asymptomatic, but serious cases can lead to fever and vomiting, and in some instances, organ failure or death. The study, published Thursday in Cell, identifies a specific scent emitted from both Zika- and dengue-infected mice that makes them more attractive to mosquitos than those without the viruses. It also points to a potential route to neutralize the olfactory flag. “This is a highly, highly influential study,” said Nikolaos Vasilakis, a professor of pathology at the University of Texas Medical Branch in Galveston who was not involved with the research. “I’m pretty sure it’s going to foster or spin off several new lines of experimentation to get a better understanding of what’s happening in humans.” In the experiments, performed at Tsinghua University in Beijing, mosquitos in a cage could enter a chamber with virus-infected mice or one with healthy mice. The mosquitos had no preference among the mice when the experimental group was newly infected, but on days four and six of infection, around 70% of the mosquitos flew to the infected group.  “An essential scientific question is how mosquitoes effectively orient to viremic hosts with a high frequency,” lead author Gong Cheng wrote in an email. Body temperature, carbon dioxide levels, and scent are all known factors in attracting mosquitos to a host. The researchers isolated each factor in repeated experiments to systematically eliminate temperature and carbon dioxide and identify scent as the attractant.

To determine exactly what caused the change in scent, they analyzed hundreds of potential volatile compounds emitted from the sick mice and narrowed it down to one, called acetophenone. The amount of acetophenone on the infected mice was found to be 10 times higher than on the uninfected ones. “Regarding virus-induced changes in behavior, this study is like a unicorn because of how in-depth they were able to go on all these levels,” said Megan Wise de Valdez, an associate professor of biology at Texas A&M in San Antonio, who was also not involved. She said the study’s methodology was so rigorous she plans to teach it in the classroom. Still, when it comes to results, “a mouse is a mouse is a mouse is a mouse,” said Vasilakis — meaning the stronger insights come from looking at humans. So the researchers took it a step further.  They applied acetophenone to human hands and found it had a similar effect in attracting mosquitos. And after finding that dengue patients were putting out higher levels of acetophenone than healthy people, they collected odors from the armpits of both and applied the scent extracts to filter paper. The perfumed papers were stuck to a human volunteer’s hand in the trapping chambers. Those with the odors of dengue patients attracted more mosquitos. After pinpointing the cause of the increased attraction, the researchers tested a possible solution. They’d found that when viruses like Zika or dengue invade the body, they suppress a particular antimicrobial protein on the skin that controls acetophenone. Researchers were able to reactivate that protein and stop the overproduction of acetophenone by feeding the mice isotretinoin, a vitamin A derivative often used as acne medication. After that, mosquitos fed on the treated mice less than the untreated mice. “If that holds in longitudinal studies, then there is hope that this is going to be an extremely effective tool in the arsenal that we have against infectious diseases,” said Vasilakis. The researchers will focus their next studies on both the host — by testing potential treatments to suppress acetophenone in human dengue patients — and the vector, by searching for the genetic key in mosquitos that identifies and seeks the acetophenone, and attempting to remove it. In the global effort to fight the viruses, this research lays new groundwork. But it will likely take years to decades before we have a solution as simple as a pill for patients to ward off hungry mosquitos.

Research Published in Cell (June 30, 2022):

https://www.sciencedirect.com/science/article/abs/pii/S0092867422006419 

Scientists have detected Zika virus RNA in free-ranging African bats. RNA, or ribonucleic acid, is a molecule that plays a central role in the function of genes. A team of Colorado State University scientists, led by veterinary postdoctoral fellow Dr. Anna Fagre, has detected Zika virus RNA in free-ranging African bats. RNA, or ribonucleic acid, is a molecule that plays a central role in the function of genes.  According to Fagre, the new research is a first-ever in science. It also marks the first time scientists have published a study on the detection of Zika virus RNA in any free-ranging bat. The findings have ecological implications and raise questions about how bats are exposed to Zika virus in nature. The study was recently published in Scientific Reports, a journal published by Nature Research. Fagre, a researcher at CSU's Center for Vector-Borne Infectious Diseases, said while other studies have shown that bats are susceptible to Zika virus in controlled experimental settings, detection of nucleic acid in bats in the wild indicates that they are naturally infected or exposed through the bite of infected mosquitoes. "This provides more information about the ecology of flaviviruses and suggests that there is still a lot left to learn surrounding the host range of flaviviruses, like Zika virus," she said. Flaviviruses include viruses such as West Nile and dengue and cause several diseases in humans. CSU Assistant Professor Rebekah Kading, senior author of the study, said she, Fagre and the research team aimed to learn more about potential reservoirs of Zika virus through the project.

The team used 198 samples from bats gathered in the Zika Forest and surrounding areas in Uganda and confirmed Zika virus in four bats representing three species. Samples used in the study date back to 2009 from different parts of Uganda, years prior to the large outbreaks of Zika virus in 2015 to 2017 in North and South Americas. "We knew that flaviviruses were circulating in bats, and we had serological evidence for that," said Kading. "We wondered: Were bats exposed to the virus or could they have some involvement in transmission of Zika virus?" The virus detected by the team in the bats was most closely related to the Asian lineage Zika virus, the strain that caused the epidemic in the Americas following outbreaks in Micronesia and French Polynesia. The first detection of the Asian lineage Zika virus in Africa was in late 2016 in Angola and Cape Verde. "Our positive samples, which are most closely related to the Asian lineage Zika virus, came from bats sampled from 2009 to 2013," said Fagre. "This could mean that the Asian lineage strain of the virus has been present on the African continent longer than we originally thought, or it could mean that there was a fair amount of viral evolution and genomic changes that occurred in African lineage Zika virus that we were not previously aware of."

Fagre said the relatively low prevalence of Zika virus in the bat samples indicates that bats may be incidental hosts of Zika virus infection, rather than amplifying hosts or reservoir hosts. "Given that these results are from a single cross-sectional study, it would be risky and premature to draw any conclusions about the ecology and epidemiology of this pathogen, based on our study," she said. "Studies like this only tell one part of the story." The research team also created a unique assay for the study, focusing on a specific molecular component that flaviviruses possess called subgenomic flavivirus RNA, sfRNA. Most scientists that search for evidence of Zika virus infection in humans or animals use PCR, polymerase chain reaction, to identify bits of genomic RNA, the nucleic acid that results in the production of protein, said Fagre.

Kading said her team will continue their research to try and learn more about how long these RNA fragments persist in tissues, which will allow them to approximate when these bats were infected with Zika virus. "There is always a concern about zoonotic viruses," she said. "The potential for another outbreak is there and it could go quiet for a while. We know that in the Zika forest, where the virus was first found, the virus is in non-human primates. There are still some questions with that as well. I don't think Zika virus has gone away forever."

See Scientific Reports (April 26, 2021):

https://doi.org/10.1038/s41598-021-87816-5 

A combination of the Zika virus and Chikungunya, two mosquito-borne infections, increase stroke risk, a new study reports. University of Liverpool researchers and Brazilian collaborators have been investigating the link between neurological disease and infection with the viruses Zika and chikungunya. These viruses, which mostly circulate in the tropics, cause large outbreaks of rash and fever in places like Brazil and India. Zika is widely known to cause brain damage in babies following infection in pregnancy, but the new research shows it can also cause nervous system disease in adults. The study of 201 adults with new onset neurological disease, treated in Brazil during the 2015Zika and 2016 chikungunya epidemics, is the largest of its kind to describe the neurological features of infection for several arboviruses circulating at the same time. The new research shows that each virus can cause a range of neurological problems. Zika was especially likely to cause Guillain-Barre syndrome, in which the nerves in the arms and legs are damaged. Chikungunya was more likely to cause inflammation and swelling in the brain (encephalitis) and spinal cord (myelitis). However, stroke, which could be caused by either virus alone, was more likely to occur in patients infected with the two viruses together.

Stroke occurs when one of the arteries supplying blood to the brain becomes blocked. The risk of stroke is known to be increased after some types of viral infection, like varicella zoster virus, which causes chickenpox and shingles, and HIV. Stroke is also being recognised increasingly as a complication of COVID-19. This has important implications for the investigation and management of patients with viral infection, as well as for understanding the mechanisms of disease. In total 1410 patients were screened and 201 recruited over a two-year period at Hospital da Restauração in Recife, Brazil. Comprehensive PCR and antibody testing for viruses was carried out in Fiocruz laboratories. Of the 201 patients admitted with suspected neurological disease linked to Zika, chikungunya or both, 148 had confirmation of infection on laboratory testing, around a third of whom had infection with more than one virus. The median age of patients was 48, and just over half the patients were female. Only around 10% patients had fully recovered at discharge, with many having ongoing issues like weakness, seizures, and problems in brain function. Of the stroke patients, who were aged 67 on average, around two thirds had infection with more than one virus.

Many of the people who had a stroke had other stroke risk factors, such as high blood pressure, indicating that stroke following Zika and chikungunya viral infection may most often be seen in those who are already high risk. Dr Maria Lúcia Brito Ferreira, neurologist and head of department at Hospital da Restauração, leading the Brazilian team said: “Zika infection most often causes a syndrome of rash and fever without many long-term consequences, but these neurological complications — although rare — can require intensive care support in hospital, often result in disability, and may cause death.” ..

Original Study Published in The Lancet Neurology (October 2020):

https://doi.org/10.1016/S1474-4422(20)30232-5

A new study led by scientists at the Walter Reed Army Institute of Research has shown for the first time that a single dose of an experimental Zika vaccine in a dengue-experienced individual can boost pre-existing flavivirus immunity and elicit protective cross-neutralizing antibody responses against both Zika and dengue viruses. Findings were published today in Nature Medicine. Researchers analyzed the antibody responses of a dengue-experienced volunteer who participated in a Phase 1 clinical trial of the WRAIR-developed Zika purified inactivated virus vaccine. They identified a potent cross-reactive antibody called MZ4 that demonstrated a potent ability to neutralize the Zika virus as well as the dengue virus serotype-2 strain. In addition, MZ4 protected against Zika and dengue in a mouse model of infection. 

"Rapid-onset countermeasures are needed to protect military personnel, travelers and residents in areas where emerging infections such as Zika and dengue viruses are already widespread and expanding," said Dr. Kayvon Modjarrad, who leads the U.S. Army Zika vaccine program, directs the Emerging Infectious Diseases Branch at WRAIR and is one of the lead authors on the paper. "These results demonstrate the potential for MZ4 to be part of the prevention toolbox for these diseases." The individual's immune profile was compared to trial volunteers who had no previous exposure to dengue virus. While the volunteer with prior dengue exposure experienced a sharp increase in antibodies that neutralize Zika and dengue viruses, following just one dose of the ZPIV vaccine, the dengue-naïve trial participants required two vaccinations to reach a similar magnitude of Zika antibody responses. Additionally, no cross-reactive antibody response to dengue virus. 

"These new findings indicate that an effective Zika vaccine could both boost dengue virus immune responses and generate potent Zika neutralizing antibodies that might have unique potential as a prevention tool in regions where both dengue and Zika are prevalent," said Dr. Shelly Krebs, a B cell researcher at WRAIR and senior author of the paper....

Published in Nat. Medicine (February 3, 2020):

https://doi.org/10.1038/s41591-019-0746-2

Researchers from The University of Texas Medical Branch at Galveston showed, for the first time, that a single, higher dose of vaccination to a pregnant mouse safely protects both her and her fetus from the Zika virus. The researchers found that a single, less potent dose was not enough to protect the fetus. The findings are currently available in Nature Communications.

"Preventing birth defects in developing fetuses is an important goal of the Zika virus vaccine but studies on vaccinations in pregnant females have been lacking, raising a number of important questions that are critical to the clinical development and regulatory approval of Zika vaccines," said UTMB's Pei-Yong Shi, senior author and the I.H. Kempner professor at the department of biochemistry and molecular biology. "Could vaccination during pregnancy protect against infection and transmission to the fetus? Does pregnancy affect immune responses to Zika vaccination? Does maternal immunity from vaccination during pregnancy protect newborns against infection?"

Shi and his laboratory previously developed a Zika vaccine and continue studies to improve its efficacy. In addition to protecting both mother and fetus, Shi said that the researchers also learned that their live-attenuated vaccine has an excellent safety profile in pregnant female mice and her fetus. For example, they saw no adverse effects on pregnancy, fetal development or infant behavior. They also found that pregnancy weakens the mother's immune response to the vaccination, suggesting that that a higher dose of the vaccine or a more immunogenic vaccine is needed during pregnancy. Taken together, their results suggest that their vaccine may be considered for both pregnant and non-pregnant people.

Published in Nature Communications (12 Dec. 2019):

https://doi.org/10.1038/s41467-019-13589-1

An international team of scientists have reported an effective and environmentally sustainable way to block the transmission of mosquito-borne dengue virus, in trials carried out in Malaysia. The breakthrough has major implications for countries with hot climates such as island nations in the South Pacific to Saudi Arabia, Africa and South America, all of which experience dengue, Zika, yellow fever and chikungunya.

Using a strain of the bacteria Wolbachia, which inhibit mosquitoes from transmitting viruses to humans, researchers at the Universities of Melbourne and Glasgow and the Institute for Medical Research in Malaysia were able to successfully reduce cases of dengue at sites in Kuala Lumpur. Their data, published today in Current Biology, shows that mosquitoes carrying the wAlbB strain of Wolbachia, when released into the wild, had the effect of reducing the incidence of dengue cases by 40 per cent. Previously, scientists including Professor Ary Hoffmann from the University of Melbourne, have carried out successful mosquito releases using a different strain of the Wolbachia bacteria, but while this strain was able to invade wild populations in some conditions, it did not appear to be suitable for use in the very hot conditions experienced in equatorial countries such as Malaysia. 

Now, this international team of researchers from Melbourne, Glasgow and Malaysia has shown that the wAlbB strain of Wolbachia is stable and effective, even in daily peak temperatures of 36°Celsius and higher, as commonly experienced in areas of Malaysia where dengue is prevalent. Professor Hoffmann, from Melbourne University's Bio21 Institute, said the findings could make a difference to a number of countries who have dengue. "This study provides us with a new Wolbachia strain for field release and highlights disease impact within a complex urban setting where dengue incidence rates are high. The intervention succeeded despite ongoing pesticide applications and other challenges that can make it hard for the Wolbachia to become established. The approach holds promise not only in Malaysia but also in other countries."

Each year there are around 90 million symptomatic cases of dengue, with severe disease in around 1 per cent of cases, including life-threatening haemorrhage or shock syndrome. In Malaysia alone, over 100,000 dengue cases were reported in 2016, with an annual cost estimated at $US175 million. Researchers released batches of Aedes aegypti mosquitoes carrying the wAlbB strain of Wolbachia into the wild, in six different sites in greater Kuala Lumpur with high levels of dengue transmission. The Wolbachia carrying mosquitoes - both male and female - then went on to mate with the wild mosquito population, resulting in the spread and establishment of the virus-inhibiting bacteria. In some sites, Wolbachia-carrying mosquitoes were measured at over 90 per cent frequency more than a year after the mosquito releases ended....

Published in Current Biology (November 21, 2019):

https://doi.org/10.1016/j.cub.2019.11.007

A new study led by researchers at Baylor College of Medicine revealed how in utero Zika virus infection can lead to microcephaly in newborns. The team discovered that the Zika virus protein NS4A disrupts brain growth by hijacking a pathway that regulates the generation of new neurons. The findings point at the possibility of developing therapeutic strategies to prevent microcephaly linked to Zika virus infection. The study appears today in the journal Developmental Cell.

Patients with rare genetic mutations shed light on how Zika virus causes microcephaly

"The current study was initiated when a patient presented with a small brain size at birth and severe abnormalities in brain structures at the Baylor Hopkins Center for Mendelian Genomics (CMG), a center directed by Dr. Jim Lupski, professor of pediatrics, molecular and human genetics at Baylor College of Medicine and attending physician at Texas Children's Hospital," said Dr. Hugo J. Bellen, professor at Baylor, investigator at the Howard Hughes Medical Institute and Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. This patient and others in a cohort at CMG had not been infected by Zika virus in utero. They had a genetic defect that caused microcephaly. CMG scientists determined that the ANKLE2 gene was associated with the condition. Interestingly, a few years back the Bellen lab had discovered in the fruit fly model that ANKLE2 gene was associated with neurodevelopmental disorders. Knowing that Zika virus infection in utero can cause microcephaly in newborns, the team explored the possibility that Zika virus was mediating its effects in the brain via ANKLE2.

In a subsequent fruit fly study, the researchers demonstrated that overexpression of Zika protein NS4A causes microcephaly in the flies by inhibiting the function of ANKLE2, a cell cycle regulator that acts by suppressing the activity of VRK1 protein.

The fruit fly helps clarify the mystery

The team found that fruit fly larvae with mutations in ANKLE2 gene had small brains with dramatically fewer neuroblasts—brain cell precursors—and could not survive into adulthood. Experimental expression of the normal human version of ANKLE2 gene in mutant larvae restored all the defects, establishing the loss of Ankle2 function as the underlying cause. "To understand why ANKLE2 mutants have fewer neuroblasts and significantly smaller brains, we probed deeper into asymmetric cell divisions, a fundamental process that produces and maintains neuroblasts, also called neural stem cells, in the developing brains of flies and humans," said first author Dr. Nichole Link, postdoctoral associate in the Bellen lab. Asymmetric cell division is an exquisitely regulated process by which neuroblasts produce two different cell types. One is a copy of the neuroblast and the other is a cell programmed to become a different type of cell, such as a neuron or glia. Proper asymmetric distribution and division of these cells is crucial to normal brain development, as they need to generate a correct number of neurons, produce diverse neuronal lineages and replenish the pool of neuroblasts for further rounds of division.

"When flies had reduced levels of Ankle2, key proteins, such as Par complex proteins and Miranda, were misplaced in the neuroblasts of Ankle2 larvae. Moreover, live imaging analysis of these neuroblasts showed many obvious signs of defective or incomplete cell divisions. These observations indicated that Ankle2 is a critical regulator of asymmetric cell divisions," said Link....

Published on Developmental Cell (November 14, 2019):

https://doi.org/10.1016/j.devcel.2019.10.009

When scientists discovered that the Zika virus can survive in semen for up to 6 months, people exposed to the disease—especially those hoping to have children—were horrified. It’s now known that the virus can be sexually transmitted up to 41 days. Now, a new meta-analysis has found that 26 other viruses can also live in human semen and go on to infect the bloodstream. Those include the viruses that cause Ebola, HIV, hepatitis B, and herpes. After reviewing more than 3800 scientific publications, the authors also found evidence that at least 11 viruses can live in the testes, including those that cause influenza, dengue, and severe acute respiratory syndrome. 

These viruses could potentially be found in semen, too, the authors say. Though not all 27 viruses are capable of person-to-person transmission, they can have other serious consequences, like reducing fertility or increasing the risk of acquiring a sexually transmitted disease. Some of these viruses can even cause mutations in the DNA of sperm, which could then fertilize an egg and pass along the virus-induced mutations to future generations. 

The findings, published last week in the Centers for Disease Control and Prevention’s Emerging Infectious Diseasesjournal, suggest that more viruses can live in semen than previously thought.  But the authors warn that far more research is needed to understand how and whether the viruses can be sexually transmitted and exactly which viruses remain viable in semen, for how long, and at what concentrations. 

Original findings published in the journal Emerging Infectious Diseases:

https://doi.org/10.3201/eid2311.171049

Table of viruses found in semen available at:

https://wwwnc.cdc.gov/eid/article/23/11/17-1049-t1

Just when international fears of contracting Zika began to fade in 2017, an undetected outbreak was peaking in Cuba—a mere 300 miles off the coast of Miami. A team of scientists at Scripps Research, working in concert with several other organizations, uncovered the hidden outbreak by overlaying air-travel patterns with genomic sequencing of virus samples from infected travelers. The discovery is featured on the cover of the Aug. 22 issue of Cell.

"Infectious diseases such as Zika are global problems, not local problems, and greater international collaboration and coordination is critical if we are to stay ahead of looming threats," says Kristian Andersen, Ph.D., associate professor at Scripps Research and director of Infectious Disease Genomics at the Scripps Research Translational Institute. "Through this study, we developed a framework for a more global, more proactive way of understanding how viruses are spreading. The traditional reliance on local testing may not always be sufficient on its own." Scripps Research partnered on this project with Yale University, Florida Gulf Coast University, the Florida Department of Health, and many other organizations.

However, Andersen and his collaborators found that an undetected outbreak was reaching its peak in Cuba at that time, off the radar of international health agencies. Surprisingly, the outbreak lagged other Caribbean countries by a year, likely due to an aggressive mosquito-control campaign that delayed the disease's emergence, according to the study. The researchers noted that other infectious diseases spread by Aedes aegypti mosquitoes, including dengue, also were absent in Cuba at the same time. Andersen's team had no idea it would expose an unknown outbreak when it began investigating travel-associated Zika cases in 2017. The scientists simply wanted to know if the epidemic really was winding down. Instead, they found that a steady number of travelers from the Caribbean were still contracting the virus. With limited access to reliable local case reporting, the team devised a way to estimate local prevalence by obtaining blood samples from infected travelers who had visited Cuba, then using genomic sequencing to reconstruct virus ancestry and outbreak dynamics. The approach is known as "genomic epidemiology." By examining tiny genomic changes in each virus sample, Gangavarapu was able to determine a "clock rate" to reveal the age of the virus. The timeline determined that the outbreak in Cuba was established a year later than other outbreaks in the Caribbean. "We realized there was a whole outbreak that had gone undetected," Gangavarapu says.

Findings were published in Cell on August 22, 2019:

https://doi.org/10.1016/j.cell.2019.07.018

Seventy-one of 110 Brazilian infants at the highest risk for experiencing problems due to exposure to the Zika virus in the womb experienced a wide spectrum of brain abnormalities, including calcifications and malformations in cortical development.  The infants were born at the height of Brazil's Zika epidemic, a few months after the nation declared a national public health emergency. Already, many of the infants had been classified as having the severe form of congenital Zika syndrome, and many had microcephaly, fetal brain disruption sequence, arthrogryposis and abnormal neurologic exams at birth. These 110 infants "represented a group of ZIKV-exposed infants who would be expected to have a high burden of neuroimaging abnormalities, which is a difference from other reported cohorts," Sarah B. Mulkey, M.D., Ph.D., writes in an invited commentary published in JAMA Network Open that accompanies the Rio de Janeiro study.

Indeed, a retrospective cohort of 82 women exposed to Zika during their pregnancies led by a research team at Children's National found only three pregnancies were complicated by severe fetal brain abnormalities. Compared with the 65% abnormal computed tomography (CT) or magnetic resonance imaging (MRI) findings in the new Brazilian study, about 1 in 10 (10%) of babies born to women living in the continental U.S. with confirmed Zika infections during pregnancy had Zika-associated birth defects, according to the Centers for Disease Control and Prevention.

"Centered on the findings of Pool, et al, and others, early neuroimaging remains one of the most valuable investigations of the Zika-exposed infant," Dr. Mulkey writes, including infants who are not diagnosed with congenital Zika syndrome. She recommends:

• Cranial ultrasound as the first-line imaging option for infants, if available, combined with neurologic and ophthalmologic exams, and brainstem auditory evoked potentials
• Zika-exposed infants with normal cranial ultrasounds do not need additional imaging unless they experience a developmental disturbance
• Zika-exposed infants with abnormal cranial ultrasounds should undergo further neuroimaging with low-dose cranial CT or brain MRI.

New UCLA-led research suggests that 32% of children up to the age of 3 years who were exposed to the Zika virus during the mother's pregnancy had below-average neurological development. The study also found that less than 4 percent of 216 children evaluated had microcephaly—a smaller-than-normal head that is one of the hallmarks of the mosquito-borne disease. The heads of two of those children grew to normal size over time, the researchers reported.

The findings, conducted by UCLA researchers with colleagues in Rio de Janeiro, Brazil, where the disease was first detected, as well as in Austria and Germany, are a follow-up to previous research. That study showed substantial neurologic damage identified through developmental testing and neuroimaging in children younger than age two whose mothers were infected with Zika during their pregnancies.

The researchers tested 146 children using the Bayley-III test, an extended neurodevelopmental assessment that checks language, cognitive and motor development. They used the Hammersmith Infant Neurologic Evaluation, or HINE, a less detailed assessment, on the 70 other children whose parents did not wish to take their children in for the lengthy Bayley-III. The researchers found that in the Bayley-III group, 51 children tested for language, 14 tested for cognitive development, and 24 evaluated for motor development scored below average.

The study was published in Nature Medicine today:

https://doi.org/10.1038/s41591-019-0496-1

A study led by Brazilian researchers shows that people who have had the Zika virus run a higher risk of subsequently having severe dengue and being hospitalized. The finding is highly relevant to the development of a Zika vaccine.According to the scientific literature, a second infection by any of the four known dengue serotypes is known to be typically more severe than the first, but until now no correlation between this fact and the occurrence of other diseases had been investigated. The study is published in the journal PLOS Neglected Tropical Diseases. The mechanism that exacerbates dengue infection following a case of Zika differs from that of two consecutive infections by the dengue virus, the authors conclude. The viral load is higher in the second dengue episode, with high levels of inflammatory cytokines not seen in Zika. Detection of other markers suggested that the increase in severity may be due to activation of T cells, key parts of the immune system that help produce antibodies, in a pathogenic immune response that has been termed the "original antigenic sin." The process involves so-called T-cell memory, a response in which T cells produced during a previous infection stimulate the production of more T cells to combat a new infection. Because these new cells are not specific to the virus, they trigger an excessive release of inflammatory cytokines, which attack the organism's proteins and tissues, potentially leading to hemorrhage.

The researchers analyzed samples from 1,043 laboratory-confirmed dengue patients, identifying those with prior Zika and dengue infections. The cases occurred in 2019 in São José do Rio Preto, a large city in São Paulo state, Brazil, considered hyperendemic for dengue since more than 70% of the population has had the disease. Its climate and geography favor the circulation of arboviruses throughout the year. Dengue epidemics occurred there in 2010, 2013, 2015, 2016 and 2019, with a record number of cases involving serotype 2. "We concluded that a prior dengue infection was not a risk factor for severity, probably because the patients were already into their third or fourth infection. Prior Zika infection, however, was important and an aggravating factor in a second dengue episode. This led us to suggest novel mechanisms and renew our knowledge of the natural history of the disease," Cássia Fernanda Estofolete, an infectious disease specialist at the São José do Rio Preto Medical School (FAMERP) and first author of the article, told Agência FAPESP. "Our findings confirmed the results of a previous study involving children who had Zika in Nicaragua. Later, when they had dengue, the risk of severity increased. We showed the same thing [risk of severe dengue increased by prior Zika or dengue] for adults in Brazil. We also showed that ADE [antibody-dependent enhancement, in which—instead of providing protection—antibodies enhance viral entry into host cells and can exacerbate the disease] is non-classical," said corresponding author Maurício Lacerda Nogueira. "This raises questions about the type of Zika vaccine that should be used and the optimal timing: should it be administered with a dengue vaccine in order to avoid this problem of one following the other, for example? There are various possibilities, which need to be understood to ensure correct prescription. In Brazil, it's still more important to give the dengue vaccine first because of the number of cases," added Nogueira.

Published in PLOS Neglected Diseases:

https://doi.org/10.1371/journal.pntd.0011710

Mosquito-borne viruses increasingly threaten human populations due to accelerating changes in climate, human and mosquito migration, and land use practices. Over the last three decades, the global distribution of dengue has rapidly expanded, causing detrimental health and economic problems in many areas of the world. To develop effective disease control measures and plan for future epidemics, there is an urgent need to map the current and future transmission potential of dengue across both endemic and emerging areas. Expanding and applying Index P, a previously developed mosquito-borne viral suitability measure, we map the global climate-driven transmission potential of dengue virus transmitted by Aedes aegypti mosquitoes from 1981 to 2019. This database of dengue transmission suitability maps and an R package for Index P estimations are offered to the public health community as resources towards the identification of past, current and future transmission hotspots. These resources and the studies they facilitate can contribute to the planning of disease control and prevention strategies, especially in areas where surveillance is unreliable or non-existent.

Preprint in medRxiv (Nov. 5, 2022):

https://doi.org/10.1101/2022.11.04.22281958 

LA JOLLA, CA-;Researchers at La Jolla Institute for Immunology (LJI) have found that Zika virus can mutate to become more infective-;and potentially break through pre-existing immunity.  "The world should monitor the emergence of this Zika virus variant," says LJI Professor Sujan Shresta, Ph.D., who co-led the Cell Reports study with Professor Pei-Yong Shi, Ph.D., of the University of Texas Medical Branch (UTMB). Zika virus is carried by mosquitoes, and the symptoms of Zika infection are usually mild in adults. However, the virus can infect a developing fetus, resulting in birth defects such as microcephaly. Zika virus and dengue virus overlap in many countries worldwide. Like Zika, dengue virus is a mosquito-borne flavivirus, and thus shares many biological properties. In fact, the viruses are similar enough that the immune response sparked by prior dengue exposure can offer protection against Zika.  Unfortunately, both viruses are also quick to mutate. "Dengue and Zika are RNA viruses, which means they can change their genome," explains Shresta. "When there are so many mosquitoes and so many human hosts, these viruses are constantly moving back and forth and evolving.

To study Zika's fast-paced evolution, the LJI team recreated infection cycles that repeatedly switched back and forth between mosquito cells and mice. This work gave the LJI scientists a window into how Zika virus naturally evolves as it encounters more hosts. The researchers found it is relatively easy for Zika virus to acquire a single amino acid change that allows the virus to make more copies of itself-;and help infections take hold more easily. This mutation (called NS2B I39V/I39T mutation) boosts the virus's ability to replicate in both mice and mosquitoes. This Zika variant also showed increased replication in human cells.  "This single mutation is sufficient to enhance Zika virus virulence," says study first author Jose Angel Regla-Nava, Ph.D., former postdoctoral researcher at LJI and current Associate Professor at the University of Guadalajara, Mexico. "A high replication rate in either a mosquito or human host could increase viral transmission or pathogenicity-;and cause a new outbreak." Adds Shresta, "The Zika variant that we identified had evolved to the point where the cross-protective immunity afforded by prior dengue infection was no longer effective in mice.

Unfortunately for us, if this variant becomes prevalent, we may have the same issues in real life." So how can we prepare for this kind of variant? Shresta's laboratory is already looking at ways to tailor Zika vaccines and treatments that counteract this dangerous mutation. She will also continue to work closely with Regla-Nava to better understand exactly how this mutation helps Zika replicate more efficiently. "We want to understand at what point in the viral life cycle this mutation makes a difference," says Shresta.

Research cited published in Cell Reports (April 12, 2022):

https://doi.org/10.1016/j.celrep.2022.110655 

NIH preclinical study suggests FDA-approved tetracycline-based antibiotics may slow infection and reduce neurological problems. In 2015, hundreds of children were born with brain deformities resulting from a global outbreak of Zika virus infections. Recently, National Institutes of Health researchers used a variety of advanced drug screening techniques to test out more than 10,000 compounds in search of a cure. To their surprise, they found that the widely used antibiotic methacycline was effective at preventing brain infections and reducing neurological problems associated with the virus in mice. In addition, they found that drugs originally designed to combat Alzheimer’s disease and inflammation may also help fight infections.  “Around the world, the Zika outbreak produced devastating, long-term neurological problems for many children and their families. Although the infections are down, the threat remains,” said Avindra Nath, M.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study published in PNAS(link is external). “We hope these promising results are a good first step to preparing the world for combating the next potential outbreak.” The study was a collaboration between scientists on Dr. Nath’s team and researchers in laboratories led by Anton Simeonov, Ph.D., scientific director at the NIH’s National Center for Advancing Translational Sciences (NCATS) and Radhakrishnan Padmanabhan, Ph.D., Professor of Microbiology & Immunology, Georgetown University Medical Center(link is external), Washington, D.C.

A study of Nicaraguan children links prior Zika virus infection with aggravated dengue fever symptoms. The 2015–16 Zika virus epidemic that spread through Central and South America was followed last year by a surge in dengue virus cases. While this unfortunate series of diseases battered the region’s populace, it gave scientists, who had been following a cohort of several thousand children in the area, the opportunity to study how these two flaviviruses might jointly affect the immune system. That research has revealed that kids infected with dengue virus are more likely to suffer worse symptoms if they had previously been infected with Zika than if they hadn’t. The findings, reported in Science today (August 27), indicate that antibody-dependent enhancement—a phenomenon known for making a second infection with a virus worse than the first—is not limited to influencing infections by the same pathogen. This raises concerns that such cross-species effects may occur for other types of viruses—including coronaviruses—and may impact vaccine safety, scientists say.

“It’s a pretty amazing story. [It] addresses what I think is the most important question in the field that has emerged following the Zika virus outbreak, and that is, how do Zika virus and dengue virus influence each other?” says virologist Jean Lim of the Icahn School of Medicine at Mount Sinai who was not part of the research team. Dengue and Zika viruses are closely related members of the flavivirus genus and are both transmitted to humans via the bites of infected mosquitoes. Dengue virus infection can be asymptomatic or can cause symptoms such as fever, headache, muscle aches, and rash. In some cases the disease can be severe, causing hemorrhagic fever and even shock (a dangerous drop in blood pressure). Zika virus causes a mostly mild disease—characterized by fever, rash, and joint pain—that resolves within a week, but in adults it can occasionally cause Guillain-Barré syndrome, an autoimmune condition affecting the peripheral nerves, and in pregnant women, the virus can lead to brain defects in the developing fetus including microcephaly. 

There are four strains, or serotypes, of dengue virus and infection by one type has a curious effect on infection by another, explains epidemiologist Isabel Rodriguez-Barraquer of the University of California (UC), San Francisco, who also did not work on the project. While an infection with the same serotype twice will not cause disease the second time around, if a different serotype causes the second infection, the existing antibodies fail to neutralize the virus and actually assist its entry into host cells. “The antibodies that your body builds after that first infection make the second infection worse and that’s often referred to as antibody-dependent enhancement,” Rodriquez-Barraquer says. This phenomenon is also thought to explain the worsening of disease severity seen after dengue vaccination.  Because Zika is closely related to dengue, “when Zika came along there was a question [of whether] there was going to be some sort of immunological interaction,” says UC Berkeley’s Eva Harris. And her group was in a perfect position to provide an answer, she adds, thanks to a long-standing collaboration with scientists in Nicaragua who have been monitoring infections, measuring antibody titers, and collecting other data from a rolling cohort of children since 2004.

In an earlier study, Harris’s group had shown that dengue infections preceding the Zika outbreak that started in 2015 offered a slightly protective effect against Zika severity, at least in children. Then, in 2019, when a major epidemic of dengue infections blew through the region—the worst in Nicaragua’s history—the group looked at the reverse scenario: whether prior Zika infection influenced dengue severity.  A total of 302 children of a cohort of 3,434 were diagnosed with symptomatic dengue fever between 2019 and 2020, confirmed via PCR amplification of the virus’s genetic material. By analyzing the infection history of the cohort, the team then calculated that children who had had a prior Zika infection had a roughly 12 percent chance of developing symptomatic dengue, compared with an only a 3.5 percent chance for children that had had no prior flavivirus exposure. Children who had had one prior dengue infection had a roughly 9 percent chance of later symptomatic disease. Prior Zika or dengue infection also increased the risk that a child would experience the most severe symptoms of dengue—hemorrhagic fever and shock—compared with children who had not previously had flavivirus disease, the team showed...

Published in Science (August 28, 2020):

https://doi.org/10.1126/science.abb6143

Clinical evidence is mounting that Zika virus can contribute to Guillain-Barré syndrome which causes temporary paralysis, yet the mechanism is unknown. We investigated the mechanism of temporary acute flaccid paralysis caused by Zika virus infection in aged interferon αβ-receptor knockout mice used for their susceptibility to infection. Twenty-five to thirty-five percent of mice infected subcutaneously with Zika virus developed motor deficits including acute flaccid paralysis that peaked 8-10 days after viral challenge. These mice recovered within a week. Despite Zika virus infection in the spinal cord, motor neurons were not destroyed.

We examined ultrastructures of motor neurons and synapses by transmission electron microscopy. The percent coverage of motor neurons by boutons was reduced by 20%; more specifically, flattened-vesicle boutons were reduced by 46%, and were normalized in recovering mice. Using electromyographic procedures employed in people to help diagnose Guillain-Barré syndrome, we determined that nerve conduction velocities between the sciatic notch and the gastrocnemius muscle were unchanged in paralyzed mice. However, F-wave latencies were increased in paralyzed mice, which suggests that neuropathy may exist between the sciatic notch to the nerve rootlets. Reversible synaptic retraction may be a previously unrecognized cofactor along with peripheral neuropathy for the development of Guillain-Barré syndrome during Zika virus outbreaks.

Published in Nature Scientific Reports (20 December 2019):

https://doi.org/10.1038/s41598-019-55717-3

A new technology to produce safer 'hybrid' viruses at high volumes for use in vaccines and diagnostics for mosquito-borne diseases has been developed at The University of Queensland. Researchers from UQ and QIMR Berghofer Medical Research Institute have exploited the benign characteristics of the Binjari  virus—inert to humans—to produce 'dangerous looking' mosquito-borne viruses such as Zika and dengue, but which cannot grow in humans or animals. School of Chemistry and Molecular Biosciences' Dr. Jody Hobson-Peters said the team, led by Professor Roy Hall, began to explore this possibility after discovering new viruses in the lab. "We were originally hoping to gain insights into how mosquito-borne viral diseases evolve—viruses like Zika, yellow fever and dengue," Dr. Hobson-Peters said. "We were also hoping to discover new viruses that might be useful for biotechnology or as biological control agents. "The Binjari virus stood out, and while it grows to very high levels in mosquito cells in the lab, it's completely harmless and cannot infect humans or other vertebrate species. "And it is incredibly tolerant for genetic manipulation, allowing us to swap important genes from pathogenic viruses like Zika, West Nile and dengue into the Binjari genome. "This produces hybrid, or chimeric, viruses that physically appeared identical to the disease-causing viruses under the electron microscope, but were still unable to grow in human or animal cells."

The researchers have effectively developed a new biotechnology platform requiring low biocontainment, to help safely develop vaccines and diagnostics against these mosquito-borne diseases. Professor Andreas Suhrbier, from QIMR Berghofer Medical Research Institute, said the team hoped to push this technology further down the development pathway toward human applications. "The main advantage of this system is that it is safe," Professor Suhrbier said."  "These hybrids cannot infect humans, meaning that manufacture of vaccines and diagnostic reagents don't require the strict and expensive biosecurity infrastructure ordinarily needed to grow these pathogenic viruses." "The research is a testament to collaborative science—this all fell into place, with amazing collaboration within the Australian Infectious Diseases Research Centre. "It's a technology that will truly revolutionise the manufacture of vaccines—supercharging high-volume vaccine development."

Published in Science Translational Medicine (11 December 2019):

https://doi.org/10.1126/scitranslmed.aax7888

Using a relevant animal model (pigs), University of Saskatchewan researchers have shown that mild Zika virus infection in fetuses can cause abnormal brain development in apparently healthy young animals. The study, published Nov. 14 in PLOS Pathogens, provides new insights into the potential outcomes of Zika virus infection and could point to new prevention and treatment strategies to alleviate the long-term effects of Zika virus infection.

Spread by the bite of an infected Aedes species mosquito, Zika infection of pregnant mothers can lead to death and decreased brain size (microcephaly) in fetuses, leading to life-long developmental and cognitive impairment. However, there is growing concern that sub-clinical infections (showing no symptoms) in pregnant mothers can result in brain disorders and delayed neurodevelopmental abnormalities in offspring after birth. Using the pig as a model, new research at USask's Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac) has provided direct evidence to support this concern.

"We have demonstrated in a relevant animal model that mild infection in fetuses results in abnormal brain development and impaired immunity in young pigs," said VIDO-InterVac Director Dr. Volker Gerdts who also participated in the study. Some of the affected offspring also showed altered behaviour during stress. In 2016, the World Health Organization declared Zika virus a public health emergency. While this emergency declaration has been lifted, Zika infection remains a public health concern. There is currently no approved vaccine or therapy available to combat the infection. Karniychuk said a next step is to develop an animal model for the study of how to treat and cure infections such as Zika virus in utero. There are currently no in utero therapies for congenital viral infections. Earlier this year, Karniychuk was awarded $250,000 over two years by the federal New Frontiers in Research Fund to undertake this work aimed at reducing the long-term consequences of abnormalities in developing fetuses and the treatment required after birth. For almost 45 years, VIDO-InterVac has used large animal models to help understand how pathogens cause disease.

Published in PLOS Pathigens (November 14, 2019):

https://doi.org/10.1371/journal.ppat.1008038

Like an adjustable wrench that becomes the "go-to" tool because it is effective and can be used for a variety of purposes, an existing drug that can be adapted to halt the replication of different viruses would greatly expedite the treatment of different infectious diseases. Such a strategy would prevent thousands of deaths each year from diseases like dengue and Ebola, but whether it can be done has been unclear. Now, in new work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) show that repurposing an existing drug to treat viral diseases is in fact possible - potentially bypassing the decades needed to develop such a broad-spectrum drug from scratch.

In a new study published in the journal Molecular Therapy, the Temple researchers report that a drug used in the treatment of HIV also suppresses Zika virus infection. In cell and animal models, they show that the drug, called rilpivirine, stops Zika virus by targeting enzymes that both HIV and Zika virus depend on for their replication. These enzymes occur in other viruses closely related to Zika, including the viruses that cause dengue, yellow fever, West Nile fever, and hepatitis C. Dr. Khalili, a senior investigator on the new study, attributed the breakthrough work to a productive collaboration with Temple University colleagues, including Dr. Michael L. Klein, FRS, Laura H. Carnell Professor of Science and Dean of the College of Science and Technology at Temple; and Ilker K. Sariyer, DVM, PhD, and Jennifer Gordon, PhD, Associate Professors of Neuroscience at Temple's Center for Neurovirology.

Historically rare and isolated to parts of Africa and Asia, Zika virus is now present throughout the Americas and occurs in multiple other regions of the world. It has attracted increasing attention in recent years, owing to its damaging effects to the brain and nervous system. The virus is transmitted to humans by mosquitoes. Once in the body, it infects cells and replicates, typically taking up residence in cells in neural tissues. In severe cases, Zika virus infection can cause an autoimmune condition known as Guillain-Barré syndrome, which culminates in muscle paralysis. Infants born to mothers infected during pregnancy may experience delays in neurological development and may be affected by microcephaly (abnormal smallness of the head).

To replicate inside cells, Zika virus requires an enzyme called non-structural protein 5 RNA-dependent RNA polymerase (NS5 RdRp). In the new study, Dr. Sariyer showed that rilpivirine suppresses Zika virus infection in cells by blocking viral replication. Using structural biology and computational studies, Eleonora Gianti, PhD, a research assistant professor in Dr. Klein's laboratory, was able to show that rilpivirine prevents viral replication by binding specifically to the NS5 domain. Dr. Gordon's team carried out experiments in mice, in which animals were infected with Zika virus through their footpads, similar to the way a person becomes infected through a mosquito bite. Mice that become infected with Zika virus normally become very sick within about a week and eventually die. "We found, however, that when treated with rilpivirine, the animals survived," Dr. Gordon said. "Our conclusion is that rilpivirine disrupted the virus's usual course of infection."

Rilpivirine is one of several non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs that have been developed for the treatment of HIV infection. Experiments in which the Temple researchers tested two other NNRTIs in Zika-infected cells revealed similar effects on viral replication, with the drugs specifically inhibiting NS5 activity.

Published on Molecular Therapy (October 11, 2019):

https://doi.org/10.1016/j.ymthe.2019.10.006

Biologists at Columbia University Vagelos College of Physicians and Surgeons have leveraged a computational method to map protein-protein interactions between all known human-infecting viruses and the cells they infect. The method, along with the data that it generated, has generated a wealth of information about how viruses manipulate the cells that they infect and cause disease. Among the study’s findings are the role of estrogen receptors in regulating Zika virus infection and how human papillomavirus (HPV) causes cancer.  The study, led by Sagi Shapira, Ph.D., assistant professor of systems biology at Columbia University Vagelos College of Physicians and Surgeons, was published today in the journal Cell.

At the molecular level, viruses invade cells and manipulate them to replicate, survive, and cause disease. Since they depend on human cells for their life cycle, one way viruses co-opt cellular machinery is through protein-protein interactions within their cell host. Similarly, cells respond to infection by initiating immune responses that control and limit viral replication – these too, depend on protein-protein interactions. To date, considerable effort has been invested in identifying these key interactions – and many of these efforts have resulted in many fundamental discoveries, some with therapeutic implications. However, traditional methods are limited in terms of scalability, efficiency, and even access. To address this challenge, Dr. Shapira and his collaborators developed and implemented a computational framework, P-HIPSTER, that infers interactions between pathogen and human proteins–the building blocks of viruses and cells.

Until now, our knowledge about many viruses that infect people is limited to their genome sequences. Yet for most viruses, little has been uncovered about the underlying biological interactions that drive these relationships and give rise to disease. “There are over 1,000 unique viruses that are known to infect people,” says Dr. Shapira. “Yet, despite their unquestionable public health importance, we know virtually nothing about the vast majority of them. We just know they infect human cells. The idea behind this effort was to systematically catalog the interactions that viruses have with the cells they infect. And, by doing so, also reveal some really interesting biology and provide the scientific community with a resource that they can use to make interesting observations of their own.” Using a novel algorithm, P-HIPSTer exploits protein structural information to systematically interrogate virus-human protein-protein interactions with remarkable accuracy. Dr. Shapira and his collaborators applied P-HIPSTer to all 1,001 human-infecting viruses and the approximately 13,000 proteins they encode. The algorithm predicted roughly 280,000 likely pairs of interacting proteins that represent a comprehensive catalog of human virus protein-protein interactions with an accuracy rate of almost 80 percent....

Findings publisehd on August 29, 2019 in the journal Cell:

https://doi.org/10.1016/j.cell.2019.08.005

An initial infection with dengue virus did not prime monkeys for an especially virulent infection of Zika virus, according to a study at the University of Wisconsin-Madison. Nor did a bout with Zika make a follow-on dengue infection more dangerous. As outbreaks on Pacific islands and in the Americas in recent years made Zika virus a pressing public health concern, the Zika virus's close similarity to dengue presented the possibility that one infection may exacerbate the other. Dengue virus infections are infamous for being bad the first time around. But following infection with one of the four variants (called serotypes) of dengue with an infection by a different serotype can amplify the already dangerous symptoms—high temperature, fatigue and pain—and make dengue fever even more life-threatening.

"When that second dengue virus occurs, antibodies kind of recognize it, but not in a way that allows them to take the virus out of the system and neutralize it like normal," says Dawn Dudley, a scientist in the University of Wisconsin-Madison's Department of Pathology and Laboratory Medicine and one of the authors of the new Zika study. "Instead, they have kind of a secondary effect, where by binding to the virus loosely they actually enhance the ability of the virus to get into other cells in the body and replicate more."  The study of 21 Wisconsin National Primate Research Center macaque monkeys, in which animals infected with one virus were challenged with another within nine to 12 months, supports the human epidemiological results. "Whether it was a primary infection with one of the dengue serotypes followed by a Zika infection, or Zika first with a later dengue infection, we didn't see anything unusual in those secondary infections," says UW-Madison pathology research specialist Meghan Breitbach, also an author of the study.

But it comes with a caveat important to Zika: none of the study's monkeys were pregnant. Zika's most visible and troubling results are neurological problems in babies whose mothers were infected during pregnancy, though those complications vary widely.  Dengue fever is enhanced by an earlier dengue infection only during certain conditions dependent on the serotypes of dengue involved, whether the immune memory produced by the initial infection was relatively strong or weak, and how much the antibodies created may have faded over months or years. The complicating factors have led to caution in development of Zika and  dengue vaccines for fear of sparking more severe infections later. "Our study suggests that that is unlikely," Newman says. "But as we learn more about people whose infections come two or three years apart, we may see we need to combine a Zika vaccine with a good vaccine against all four serotypes of dengue virus to prevent enhancement of either virus"

Findings published on August 1, 2019 in PLOS Pathogen:

https://doi.org/10.1371/journal.ppat.1007766

The female mosquito needs your blood to grow her eggs. Please don’t feel singled out. She bites everyone. There is no truth to the myths that mosquitoes prefer women over men or blondes and redheads over those with darker hair. She does, however, play favorites. Type O blood seems to be the vintage of choice. Stinky feet emit a bacterium that woos famished females, as do perfumes. As a parting gift, she leaves behind an itchy bump (an allergic reaction to her saliva) and potentially something far worse: infection with one of several deadly diseases, including malaria, Zika, West Nile, dengue and yellow fever.