Tag: zika

Categories : Diseases, Syndromes and ConditionsTags :

First Detection of Zika Viral DNA in African Bats

On By ModernMedia
Image source: Ekamalev at Unsplash

Researchers have, for the first time, detected Zika virus RNA in free-ranging African bats, which indicates that the bats were previously infected with Zika virus at the time the samples were taken. 

This discovery 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 the wild. The study was led by Dr Anna Fagre, a veterinary postdoctoral fellow at Colorado State University’s Center for Vector-Borne Infectious Diseases. The findings were detailed in the journal Scientific Reports.

Dr Fagre said that 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 it was transmitted by bites from 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. Other flaviviruses that cause disease in humans include West Nile and dengue.

Wide-ranging samples

Senior author Rebekah Kading, Assistant Professor at CSU, said she, Dr Fagre and the research team were hoping the project would help them to find out more about potential reservoirs of Zika virus.

With 198 samples from bats gathered in the Zika Forest and surrounding areas in Uganda, the team confirmed Zika virus in four bats representing three species. The samples date back as far as 2009 from different parts of Uganda, which is years before the large Zika outbreaks in 2015 to 2017 in North and South America.

The Zika virus was declared a public health emergency by the World Health Organization in February 2016 owing to its association with the congenital deformities, particularly microcephaly in infants borne to the infected mothers

“We knew that flaviviruses were circulating in bats, and we had serological evidence for that,” said Prof 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 Asian lineage Zika virus was in late 2016 first detected in Africa, 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 Prof 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.”

Likely incidental hosts, not reservoirs

Prof Fagre said that the relatively low prevalence of Zika virus found indicates that bats may only 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 made an assay for the study which focuses on subgenomic flavivirus RNA, sfRNA, which flaviviruses possess. Testing for Zika normally uses PCR, polymerase chain reaction, to identify bits of genomic RNA, the nucleic acid that results in the production of protein, said Fagre.

The team’s next steps will be to characterise how long these RNA fragments persist in tissues, which will allow them to estimate how long ago these bats were infected with Zika virus, Prof Kadling said.

“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.”

Source: Colorado State University

Journal information: Fagre, A. C., et al. (2021) Subgenomic flavivirus RNA (sfRNA) associated with Asian lineage Zika virus identified in three species of Ugandan bats (family Pteropodidae). Scientific Reports. doi.org/10.1038/s41598-021-87816-5.

Categories : Immune System VaccinesTags :

Discovering Antibodies That Are Safe And Effective Against Zika

On By ModernMedia

The Zika outbreak of 2015 and 2016 left lasting consequences for children who were in the womb when their mothers were infected with the virus, and now researchers are investigating a safe vaccine that will not negatively interact with certain other viruses.

Zika is a flavivirus, a family which includes dengue, West Nile, and yellow fever virus. In order to protect against these and other pathogens, “we have the ability to make a huge diversity of antibodies, and if we get infected or vaccinated, those antibodies recognise the pathogen,” explained first author Shannon Esswein, a graduate student at the California Institute of Technology.

However, when getting sick with a virus a second time, the body’s own immune response can worsen the situation. Known as antibody-dependent enhancement (ADE), this is when the antibodies stick to the outside of the virus but not neutralising its ability to lock onto cells. This can inadvertently help the virus to infect more cells by letting it enter cells the antibodies are sticking to. A recent study sought to investigate whether this could happen with monoclonal antibody treatments for COVID.

In order to prevent ADE when creating a vaccine, knowing how antibodies adhere to a specific virus is crucial for scientists. In the case flaviviruses, this is especially important as antibodies that protect against one flavivirus may also stick to, but not protect against other flaviviruses, raising the risk of ADE. Antibodies generated in response to a Zika virus vaccine could trigger ADE, if that person is exposed to other flaviviruses such as dengue.

To understand this, the researchers looked at a portion of the flavivirus called the envelope domain III protein, which has been shown to be an important target for protective antibodies fighting flavivirus infections. They studied how those antibodies changed over time as they matured and became better able to adhere to the Zika virus. They also looked at how the antibodies cross-reacted with other flaviviruses, including the four dengue virus types. Their results showed that the Zika antibodies also tightly stick to and defend against dengue type 1, but only weakly stick to West Nile and dengue types 2 and 4. “The weak cross-reactivity of these antibodies doesn’t seem to defend against those flaviviruses, but also doesn’t induce ADE,” Esswein said. These results suggest that the envelope domain III could be a useful basis for a safe vaccine. They also described structures demonstrating how two antibodies recognise Zika and West Nile envelope domain III.

The study results demonstrate how the body mounts “a potent immune response to Zika virus,” said Esswein. Insights gained on the antibodies involved in this immune response will aid the development of new vaccines.

Source: Medical Xpress

Journal information: Shannon R. Esswein et al. Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody, Proceedings of the National Academy of Sciences (2020). DOI: 10.1073/pnas.1919269117

Categories : Antibiotics Diseases, Syndromes and ConditionsTags :

A Common Antibiotic Shows Promise for Zika Protection

On By ModernMedia

A huge search through known drug compounds showed that a common antibiotic has been shown to be effective against Zika in vitro. Zika, which causes foetal microcephaly, preferentially attacks brain stem cells. 

In order to find a compound that confers Zika protection, the researchers searched for drugs that prevent virus reproduction by blocking the activity of a protein called NS2B-NS3 Zika virus protease. This protease acts to assemble the components of new Zika viruses from protein produced by the virus’ RNA injection into a cell.

“Proteases act like scissors. Blocking protease activity is an effective strategy for counteracting many viruses,” said study leader Rachel Abrams, PhD. “We wanted to look as far and wide as possible for drugs that could prevent the protease from snipping the Zika virus polyprotein into its active pieces.”

To find out which compounds blocked the protease, hundreds of assays were conducted against three different libraries.

An initial screen of 2 000 compounds showed that common tetracycline-based antibiotic drugs, such as methacycline were able to block the protease.

A larger screen of 10 000 compounds found potential candidates in an investigational anti-inflammatory medicine, MK-591, and a failed anti-Alzheimer’s disease drug, JNJ-404.  

Finally, 130 000 compounds were screened virtually, with machine learning being used to investigate what made a good candidate.

The candidate compounds were shown to reduce Zika infections of brain stem cells in vitro.

As methacycline is known to cross the placental barrier, this emerged as a promising candidate to treat pregnant women infected with the virus. However in mouse models, treatment with methacycline only partially protected the brains of newborn mice.

“These results suggest that tetracycline-based antibiotics may at least be effective at preventing the neurological problems associated with Zika virus infections,” said Dr Abrams. “Given that they are widely used, we hope that we can rapidly test their potential in clinical trials.”

Source: News-Medical.Net