A small mutation can make Zika virus even more dangerous
How outbreaks could happen, even in areas with prior immunity
Date:
April 12, 2022
Source:
La Jolla Institute for Immunology
Summary:
Researchers have found that Zika virus can mutate to become more
infective -- and potentially break through pre-existing immunity.
FULL STORY ========================================================================== 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.
"In areas where Zika is prevalent, a vast majority of people have already
been exposed to dengue virus and have both T cells and antibodies that cross-react," says Shresta.
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.
This research was supported by the the National Institutes of Health (R01 AI153500, R01 AI163188, R56 AI148635, U01 AI151810, R01 NS106387, R01
AI134907, R43 AI145617, and UL1 TR001439), the Sealy & Smith Foundation,
the Kleberg Foundation, the John S. Dunn Foundation, the Amon G. Carter Foundation, the Gilson Longenbaugh Foundation, and the Summerfield
Robert Foundation.
========================================================================== Story Source: Materials provided by
La_Jolla_Institute_for_Immunology. Note: Content may be edited for style
and length.
========================================================================== Journal Reference:
1. Jose Angel Regla-Nava et al. A Zika Virus Mutation Enhances
Transmission
Potential and Confers Escape from Protective Dengue Virus
Immunity. Cell Reports, 2022 DOI: 10.1016/j.celrep.2022.110655 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220412141017.htm
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