Antibodies block specific viruses that cause arthritis, brain infections
Could form basis of universal therapy, vaccines for alphaviruses

Date:
August 19, 2021
Source:
Washington University School of Medicine
Summary:
Researchers have found antibodies that protect against
specific mosquito- borne viruses that cause arthritis and brain
infections. The findings could lead to a universal therapy or
vaccine for the viruses.



FULL STORY ========================================================================== Alphaviruses -- mosquito-borne viruses that can trigger brain infections
and arthritis -- may have met their match.


========================================================================== Researchers at Washington University School of Medicine in St. Louis
have identified two antibodies that protect animals from disease caused
by alphaviruses. The antibodies worked for every alphavirus tested,
meaning they potentially could form the basis of treatments or serve as
a template for a universal vaccine.

The findings are published Aug. 19 in the journal Cell.

"In the U.S., the alphavirus we worry most about is chikungunya virus,
which can cause debilitating arthritis, but we also do see cases of encephalitis caused by Eastern equine encephalitis virus," said senior
author Michael S.

Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine
and a professor of molecular microbiology and of pathology &
immunology. "Alphaviruses used to be limited to the tropics, but in
recent years they've been spreading into new geographic areas. Most
are still uncommon, but together they cause millions of infections and
a considerable burden of disease, and we don't have specific therapies
or vaccines for any of them." The alphavirus group includes more than
30 species, split into two branches.

Viruses such as chikungunya, Mayaro, O'nyong-nyong and Ross River, all of
which cause fever, rash and arthritis, historically had been limited to
Africa, Asia and Europe. However, beginning in 2013, chikungunya worked
its way into the Caribbean and parts of North and South America. The other branch of alphaviruses, found in the Americas, includes Eastern, Western
and Venezuelan equine encephalitis viruses and causes brain infections.

Diamond and colleagues previously identified a group of antibodies
that neutralize many members of the arthritis-causing branch of the
alphavirus group. But those antibodies didn't work against all of the
viruses that cause arthritis and failed entirely against the ones that
cause brain infections.

To find antibodies that would protect against the whole alphavirus group, Diamond and colleagues -- including co-first authors Arthur S. Kim,
PhD, then a graduate student, and Natasha M. Kafai, an MD/PhD student -- screened a set of antibodies produced by two people who had been infected
with chikungunya virus.

They tested the antibodies against a panel of alphaviruses representing
both branches of the group. Two antibodies recognized all of the
alphaviruses tested.

Then, they assessed whether the antibodies could prevent arthritis
or brain infection in animals. Using mice, they tested each antibody
against two alphaviruses that cause arthritis and three that cause
brain infections. Both antibodies protected the animals against all of
the viruses.

Further experiments showed that the antibodies worked by blocking
developing virus particles from exiting one cell en route to infecting
another. The antibodies attach to part of a viral protein called E1 that
is exposed only during the exiting process. Once the virus has fully
formed and detached from the cell, the E1 protein is folded into the
virus particle and hidden.

In a related paper being published in the same issue of Cell, James
E. Crowe, MD, of Vanderbilt University Medical Center, also reports that antibodies targeting the E1 protein bind to a wide range of alphaviruses, prevent them from exiting cells and protect animals against both arthritis
and brain infections. Crowe and Diamond are longtime collaborators,
and each contributed to the other's paper.

The two studies start from different points -- Diamond began with a
virus that causes arthritis; Crowe started with one that causes brain infections -- but arrive at basically the same conclusion: The E1 protein
could be the key to universal protection against alphaviruses.

"If we could figure out how to make a vaccine that targets the E1
protein effectively, it would be a cost-effective way to provide broad protection for people in resource-limited places, which is where most alphavirus infections occur," Diamond said. "It's challenging to make
such a vaccine since the target is hidden most of the time. But there
are techniques that can be used to make the immune system focus on E1
and generate a good antibody response against it.

That's the next step toward creating a universal vaccine." ========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Tamara
Bhandari. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Arthur S. Kim, Natasha M. Kafai, Emma S. Winkler, Theron
C. Gilliland,
Emily L. Cottle, James T. Earnest, Prashant N. Jethva, Paulina
Kaplonek, Aadit P. Shah, Rachel H. Fong, Edgar Davidson, Ryan
J. Malonis, Jose A.

Quiroz, Lauren E. Williamson, Lo Vang, Matthias Mack, James
E. Crowe, Benjamin J. Doranz, Jonathan R. Lai, Galit Alter,
Michael L. Gross, William B. Klimstra, Daved H. Fremont, Michael
S. Diamond. Pan-protective anti-alphavirus human antibodies target
a conserved E1 protein epitope.

Cell, 2021; 184 (17): 4414 DOI: 10.1016/j.cell.2021.07.006 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210819113051.htm

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