Viruses can steal our genetic code to create new human-virus genes


Date:
June 18, 2020
Source:
The Mount Sinai Hospital / Mount Sinai School of Medicine
Summary:
A new study unveils a novel mechanism that allows viruses to
produce unexpected proteins.



FULL STORY ==========================================================================
Like a scene out of "Invasion of the Body Snatchers," a virus infects a
host and converts it into a factory for making more copies of itself. Now researchers have shown that a large group of viruses, including the
influenza viruses and other serious pathogens, steal genetic signals
from their hosts to expand their own genomes.


==========================================================================
This finding is presented in a study published online today and in print
June 25 in Cell. The cross-disciplinary collaborative study was led by researchers at the Global Health and Emerging Pathogens Institute at Icahn School of Medicine at Mount Sinai in New York, and at the MRC-University
of Glasgow Centre for Virus Research in the UK.

The cross-disciplinary team of virologists looked at a large group of
viruses known as segmented negative-strand RNA viruses (sNSVs), which
include widespread and serious pathogens of humans, domesticated animals
and plants, including the influenza viruses and Lassa virus (the cause
of Lassa fever).

They showed that, by stealing genetic signals from their hosts,
viruses can produce a wealth of previously undetected proteins. The
researchers labeled them as UFO (Upstream Frankenstein Open reading frame) proteins, as they are encoded by stitching together the host and viral sequences. There was no knowledge of the existence of these kinds of
proteins prior to this study.

These UFO proteins can alter the course of viral infection and could be exploited for vaccine purposes.

"The capacity of a pathogen to overcome host barriers and establish
infection is based on the expression of pathogen-derived proteins,"
said Ivan Marazzi, PhD, Associate Professor of Microbiology at Icahn
School of Medicine and corresponding author on the study. "To understand
how a pathogen antagonizes the host and establishes infection, we need
to have a clear understanding of what proteins a pathogen encodes, how
they function, and the manner in which they contribute to virulence."
Viruses cannot build their own proteins, so they need to feed suitable instructions to the machinery that builds proteins in their host's cells.

Viruses are known to do this through a process called "cap-snatching,"
in which they cut the end from one of the cell's own protein-encoding
messages (a messenger RNA, or mRNA) and then extend that sequence with
a copy of one of their own genes. This gives a hybrid message to be read.

"For decades we thought that by the time the body encounters the signal
to start translating that message into protein (a 'start codon') it is
reading a message provided to it solely by the virus. Our work shows
that the host sequence is not silent," said Dr. Marazzi.

The researchers show that, because they make hybrids of host mRNAs
with their own genes, viruses (sNSVs) can produce messages with extra, host-derived start codons, a process they called "start snatching." This
makes it possible to translate previously unsuspected proteins from the
hybrid host-virus sequences.

They further show that these novel genes are expressed by influenza
viruses and potentially a vast number of other viruses. The product
of these hybrid genes can be visible to the immune system, and they
can modulate virulence. Further studies are needed to understand this
new class of proteins and what the implications are of their pervasive expression by many of the RNA viruses that cause epidemics and pandemics.

Ed Hutchinson, PhD, corresponding author and a research fellow at MRC- University of Glasgow Centre for Virus Research, said, "Viruses take
over their host at the molecular level, and this work identifies a new
way in which some viruses can wring every last bit of potential out of
the molecular machinery they are exploiting. While the work done here
focusses on influenza viruses, it implies that a huge number of viral
species can make previously unsuspected genes." Researchers say the next
part of their work is to understand the distinct roles the unsuspected
genes play. "Now we know they exist, we can study them and use the
knowledge to help disease eradication," said Dr. Marazzi. "A large
global effort is required to stop viral epidemics and pandemics, and
these new insights may lead to identifying novel ways to stop infection."
This study was supported by funders including the National Institute of
Allergy and Infectious Diseases and the UK Medical Research Council.


========================================================================== Story Source: Materials provided by The_Mount_Sinai_Hospital_/_Mount_Sinai_School_of Medicine. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Jessica Sook Yuin Ho, Matthew Angel, Yixuan Ma, Elizabeth Sloan,
Guojun
Wang, Carles Martinez-Romero, Marta Alenquer, Vladimir Roudko,
Liliane Chung, Simin Zheng, Max Chang, Yesai Fstkchyan, Sara
Clohisey, Adam M.

Dinan, James Gibbs, Robert Gifford, Rong Shen, Quan Gu, Nerea
Irigoyen, Laura Campisi, Cheng Huang, Nan Zhao, Joshua D. Jones,
Ingeborg van Knippenberg, Zeyu Zhu, Natasha Moshkina, Le'a Meyer,
Justine Noel, Zuleyma Peralta, Veronica Rezelj, Robyn Kaake,
Brad Rosenberg, Bo Wang, Jiajie Wei, Slobodan Paessler, Helen
M. Wise, Jeffrey Johnson, Alessandro Vannini, Maria Joa~o
Amorim, J. Kenneth Baillie, Emily R. Miraldi, Christopher
Benner, Ian Brierley, Paul Digard, Marta Łuksza, Andrew
E. Firth, Nevan Krogan, Benjamin D. Greenbaum, Megan K. MacLeod,
Harm van Bakel, Adolfo Garci`a-Sastre, Jonathan W. Yewdell,
Edward Hutchinson, Ivan Marazzi. Hybrid Gene Origination Creates
Human-Virus Chimeric Proteins during Infection. Cell, 2020; DOI:
10.1016/j.cell.2020.05.035 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/06/200618120213.htm

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