Protein uses two antiviral strategies to ward off infections

Date:
August 11, 2020
Source:
eLife
Summary:
To protect humans against infection, a protein called MARCH8 tags
the vesicular stomatitis virus (VSV) for destruction while it
merely holds HIV hostage, a new study shows.



FULL STORY ==========================================================================
To protect humans against infection, a protein called MARCH8 tags the
vesicular stomatitis virus (VSV) for destruction while it merely holds
HIV hostage, a new study in eLife shows.


==========================================================================
The findings reveal how a single protein can use multiple strategies
to defend cells against viral infection. They could also improve our understanding of how HIV overcomes the human immune defence.

Previous studies have shown that MARCH8 stops HIV and VSV from entering
human cells by targeting the viral proteins that are essential for
these viruses to enter cells. But how the protein does this remained
unclear. Researchers in Japan suspected that MARCH8 might flag an
important VSV envelope protein for destruction by targeting a particular
amino acid called lysine.

"The VSV G-glycoprotein (VSV-G) has a short tail containing five lysines, making it an ideal target," explains senior author Kenzo Tokunaga,
Principal Investigator in the Department of Pathology, National Institute
of Infectious Diseases, Tokyo, Japan. "The HIV envelope glycoprotein
(Env), by contrast, has a very long tail with only two lysines, making
it harder for MARCH8 to flag it for destruction." To test their idea,
Tokunaga and his team, including co-first authors and Postdoctoral Fellows Yanzhao Zhang and Takuya Tada, replaced the five lysines on the tail
of VSV-G with five arginines -- another type of amino acid. They also
replaced the two lysines on the tail of HIV Env with two arginines. The
change allowed VSV-G to escape MARCH8, but not HIV Env. This suggests
that MARCH8 targets HIV Env and VSV-G using two different mechanisms.

Instead of marking HIV Env for destruction, the team found that MARCH8
holds it hostage, inhibiting its ability to make infectious copies
of itself (replicate) and spread to other cells. When they created a
mutant version of MARCH8 that lacks a specific pattern of the amino
acid tyrosine, they found that HIV Env was able to escape, allowing the
virus to replicate. This suggests that the tyrosine pattern in MARCH8
is essential to its HIV defence strategy.

"Our work may help explain why humans don't develop symptoms when infected
with VSV, even though it can make some animals, mostly cows, horses
and pigs, very ill," says Tokunaga. "The findings might also explain,
at least in part, why HIV is able to hide from the human immune system,
causing persistent infections that are difficult to treat."

========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Yanzhao Zhang, Takuya Tada, Seiya Ozono, Satoshi Kishigami, Hideaki
Fujita, Kenzo Tokunaga. MARCH8 inhibits viral infection by two
different mechanisms. eLife, 2020; 9 DOI: 10.7554/eLife.57763 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200811120103.htm

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