Resourceful viral protein combats monkey and human defenses differently
Date:
March 24, 2022
Source:
Tokyo Medical and Dental University
Summary:
Researchers have found that different parts of viral protein U
expressed by simian immunodeficiency virus are required to bind to
and block tetherin, an antiviral protein, in monkey cells versus
in human cells.
This suggests that the virus uses two different mechanistic
strategies to evade this host defense and sheds new light on
host-pathogen coevolution.
FULL STORY ==========================================================================
In the epic battle between hosts and viruses, viruses are constantly
evolving to be more infectious. Now, researchers from Japan have found
that human genes also evolve to help protect our bodies from invasion
by life-threatening viruses.
==========================================================================
In a study published in December in Journal of Virology, researchers
from Tokyo Medical and Dental University (TMDU) have revealed that a
monkey variant of human immunodeficiency virus (HIV) can counteract a
human protein that defends against viral infection in a different way
than it counteracts the same protein in monkeys.
Simian immunodeficiency virus (SIV) is closely related to HIV, and both
viruses tend to use similar strategies to escape their hosts' defenses,
which also tend to be very similar. One of these defenses is a protein
called tetherin (also known as BST-2 or CD317). If a cell is invaded
by the virus, tetherin prevents the virus from leaving the cell and
infecting other nearby cells. To counter this measure, HIV and SIV make
a protein called viral protein U (Vpu) that attaches to tetherin and
blocks its effects.
"Because viruses adapt to their hosts, HIV Vpu is most effective against
human tetherin, while SIV Vpu is most effective against monkey tetherin," explains Dr. Takeshi Yoshida, senior author of the study. "But in at
least one unusual case, a strain of SIV that typically infects the greater spot-nosed monkey can also overcome human defenses, which suggests that
SIV potentially infects humans." To explore how SIV Vpu affects human tetherin, the researchers mutated different parts of the protein and
looked at how well it blocked tetherin's normal activities and effects.
"The results were unexpected," says Dr. Weitong Yao, lead author. "We discovered that the parts of SIV Vpu that are needed to counteract
monkey tetherin are not the same as the parts needed to counteract
human tetherin." The researchers pinpointed seven specific amino acids
(the basic building blocks of proteins) that are needed for SIV to block
human tetherin.
Importantly, these seven amino acids were not essential for the virus
to block monkey tetherin.
"What this tells us is that SIV Vpu may use a totally distinct mechanisms
to counteract the effects of monkey and human tetherin," says Yoshida.
Given the different approaches that this viral protein uses to neutralize monkey and human tetherin, it seems likely that the gene encoding human tetherin faced different pressures over the course of evolution than
the gene encoding monkey tetherin. The results from this study could
help us better understand the evolution of host genes as a result of host-pathogen interactions.
========================================================================== Story Source: Materials provided by
Tokyo_Medical_and_Dental_University. Note: Content may be edited for
style and length.
========================================================================== Journal Reference:
1. Weitong Yao, Klaus Strebel, Shoji Yamaoka, Takeshi Yoshida. Simian
Immunodeficiency Virus SIVgsn-99CM71 Vpu Employs Different
Amino Acids To Antagonize Human and Greater Spot-Nosed Monkey
BST-2. Journal of Virology, 2022; 96 (4) DOI: 10.1128/JVI.01527-21 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220324122609.htm
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