Can scientists take the STING out of common respiratory viruses?

Date:
October 26, 2020
Source:
University of North Carolina Health Care
Summary:
Scientists have made a curious discovery about a well-known
human protein that helps the immune system fight viral
infections. Researchers found that one class of viruses actually
requires this protein to infect cells and replicate.



FULL STORY ========================================================================== University of North Carolina School of Medicine scientists have made a
curious discovery about a well-known human protein that helps the immune
system fight viral infections. The lab of Stan Lemon MD, and colleagues
found that one class of viruses actually requires this protein to infect
cells and replicate.


========================================================================== Published in the Proceedings of the National Academy of Sciences, the
research reveals an Achilles heel of rhinoviruses, which account for
as much as 70% of common colds and acute wheezing episodes, and likely
account for tens of billions of dollars in health-related costs each
year in the United States.

There is no effective anti-viral treatment.

"We found that a large proportion of these rhinoviruses, particularly the
ones that cause severe disease, need a human protein called STING to make copies of its RNA," said Lemon, professor of medicine and microbiology
and immunology at the UNC School of Medicine. "We don't know how or why;
we'll have to study this further. But our work opens the door to a new
strategy for controlling infection of these pesky and at times very
dangerous pathogens." Viruses are relatively simple bugs able to infect
human cells and then replicate to cause diseases from the common cold
to COVID-19 and more dangerous pathogens, such as HIV and Ebola. Humans
have developed some defenses against these invasions, and one part of the defense is called the 'stimulator of interferon gene' protein, or STING,
so named for its ability to sense invaders and enhance our immune response
to many viruses, including herpes viruses and cytomegalovirus, a common
bug that infects half of adults by age 40 and causes symptoms similar to
many other viral infections. Rhinoviruses turn STING against us, and use
it to promote their own growth. The genomes of many viruses are made up of
DNA, whereas the genomes of rhinoviruses are composed of RNA, a similar
kind of genetic code at the foundation of all living things. STING helps
us defend against DNA viruses, but is instead helping this RNA virus.

Human rhinoviruses comprise a large group of common respiratory tract
pathogens -- dozens of different viruses -- that are associated with
asthma, pneumonia and exacerbations of chronic lung disease in both
children and adults. There are no vaccines available to prevent these
common infections because the viruses are very diverse and different from
each other in terms of how they are 'seen' by the human immune system.

"If you are immune to one, you can easily catch another," Lemon
said. "There is also no effective antiviral therapy for any of them."
Lemon's lab studies how viruses like rhinoviruses interact with human
proteins with the hope of finding a way to block or limit the interaction
and, as a result, limit symptoms and disease progression. While studying
the human proteins involved in this interaction, they found something completely unexpected. Using cell cultures, they employed experimental techniques to disable STING to see what happened. To their surprise,
the virus could not infect cells and replication was stopped.

"It could be possible to target this protein with a small molecule in
way that would benefit people with rhinoviruses, especially children
and others who can become severely ill," Lemon said.


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


========================================================================== Journal Reference:
1. Kevin L. McKnight, Karen V. Swanson, Kathryn Austgen, Cindy
Richards,
Jonathan K. Mitchell, David R. McGivern, Ethan Fritch, John
Johnson, Katja Remlinger, Michal Magid-Slav, Maryna Kapustina,
Shihyun You, Stanley M. Lemon. Stimulator of interferon genes
(STING) is an essential proviral host factor for human rhinovirus
species A and C. Proceedings of the National Academy of Sciences,
2020; 202014940 DOI: 10.1073/ pnas.2014940117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201026135750.htm

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