Texas A&M Study Offers New Virus-Host Protein Insight, New Possibilities for Antiviral Development
Posted April 05, 2018
Viruses have a very limited set of genes and, therefore, must use
the cellular machineries of their hosts for most parts of their
In a new study, scientists at Texas A&M and Uppsala
universities have discovered a specific host protein that many
viruses use for their transport within the cell.
The human gene, ZC3H11A, is found in all vertebrates and is
expressed essentially in all human cells; the gene has been known
for about 20 years, but its functional importance has been
The team, led by Texas A&M professor Leif Andersson,
however, has discovered that ZC3H11A is critical for the
replication of multiple medically important viruses—including
adenovirus, influenza virus, HIV, and herpes simplex virus—which
opens up new possibilities for the development of new
broad-spectrum antiviral therapies.
The discovery was published April 2 in the Proceedings of the
National Academy of Sciences (USA).
With modern DNA sequencing technologies, it is relatively easy
to identify all genes coding for proteins in an organism, but it is
often much more challenging to really understand the cellular
function of proteins, according Andersson, professor of animal
genomics in the Texas A&M College of Veterinary Medicine &
Biomedical Sciences’ (CVM) Department of Veterinary Integrative
Biosciences (VIBS) and professor of functional genomics at Sweden's
The discovery is the result of a project by Uppsala doctoral
student Shady Younis, who used the gene-editing tool CRISPR-Cas9 to
inactivate the ZC3H11A gene in a human cell line; initially, he
found that the inactivation of ZC3H11A had little effect, showing
that it is not essential for the growth of these human cells.
But while discussing his finding with fellow doctoral student
Wael Kamel, Younis decided to challenge the cells lacking ZC3H11A
with a virus infection.
The ZC3H11A protein (in green) surrounds the adenovirus
replication centers in human in HeLa cells. Photo by Shady
To their surprise, there was a drastic reduction of the growth
of adenovirus (a group of viruses that can infect the tissue
linings of the respiratory tract, eyes, intestines, urinary tract,
and nervous system) in the cells lacking ZC3H11A, compared with
cells expressing the protein.
The team has now demonstrated that at least four different
viruses that replicate in the host cell nucleus are dependent on
the ZC3H11A protein for their efficient growth; these viruses need
ZC3H11A for the transport of virus RNA from the nucleus to the
cytoplasm, where the virus proteins will be produced before the
viruses can exit the cell and infect other cells, Kamel said.
“This serendipitous discovery is an excellent example of how a
good scientific environment can inspire scientists to collaborative
efforts that may lead to important scientific discoveries,”
The group also has demonstrated that ZC3H11A is a stress-induced
RNA binding protein and appears to be part of a previously unknown
mechanism for how cells handle stress.
The observation that the amount of ZC3H11A protein increases
during a virus infection was a very surprising finding since
viruses typically shut down host-cell protein expression to favor
virus production, Andersson said.
“Our data suggest that nuclear-replicating viruses have hijacked
a cellular mechanism for RNA transport activated during stress for
their own advantage,” he said.
The spread of the influenza virus that has severely impacted
people around the world proves there is a strong need to develop
new antiviral drugs; a major goal for the team is now to test if
they can block how viruses take advantage of the function of the
ZC3H11A protein and if this will impair virus growth in living
animals, not only in cells as they have proven in the current
study, Andersson said.
For more information about the Texas
A&M College of Veterinary Medicine & Biomedical Sciences,
please visit our website at vetmed.tamu.edu or join us on Facebook, Instagram, and Twitter.
Contact Information: Megan Palsa, Executive Director of
Communications, Media & Public Relations, Texas A&M College
of Veterinary Medicine & Biomedical Science; firstname.lastname@example.org;
979-862-4216; 979-421-3121 (cell)
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