Viruses leave traces long after infection, research finds

Date:
August 24, 2021
Source:
University of Basel
Summary:
Viruses do not always kill the cells they infect. Researchers have
discovered in experiments with mice that cells have the power to
self- heal and eliminate viruses. However, these cells undergo
long-term changes. The findings may provide a hint as to why
cured hepatitis C patients are more susceptible to liver cancer
for years after.



FULL STORY ========================================================================== Viruses do not always kill the cells they infect. Researchers at the
University of Basel have discovered in experiments with mice that cells
have the power to self-heal and eliminate viruses. However, these cells
undergo long-term changes. The findings may provide a hint as to why cured hepatitis C patients are more susceptible to liver cancer for years after.


========================================================================== Viruses need the infrastructure of the body's cells in order to
multiply. With many types of viruses, this ultimately means death for
the affected cell if its membrane dissolves and the newly created viruses
swarm out to attack new cells.

But some viruses do not kill the cells they infect -- presumably with the
aim of maintaining the infection for as long as possible. These include hepatitis B and C viruses, which cause chronic infections in humans.

Until now, it was generally assumed that such viruses remain permanently
in the infected cells of the body. However, a research team led by
Professor Daniel Pinschewer from the University of Basel now reports in
the Journal of Experimental Medicine that this is not the case. Their experiments involved a mouse virus called lymphocytic choriomeningitis
virus (LCMV), which triggers a chronic infection in mice -- similar to hepatitis C virus in humans -- and also infects the liver.

Virus eliminated, but not without trace This model enabled the
researchers to demonstrate that the virus disappears from the infected
liver cells after a certain time period. It is not yet clear exactly
how this happens. However, the researchers were able to rule out the possibility that the cells need the support of immune cells in order to
do this. "Liver cells seem to have their own mechanism for removing a
virus from within," says Dr Peter Reuther, one of the study's two lead
authors. The chronic infection by such viruses is based on a continuous infection of new cells.

Despite the astonishing self-healing power of cells, the infection
does not pass them by without leaving a trace. As further analysis
of the healed cells showed, their genetic profile remained altered:
the same genes were no longer read in the same quantity as in those
cells that had not been subject to infection. The change particularly
affected genes related to cell division and cellular metabolism. It is
still unclear how long these changes persist, however.

Parallels with hepatitis C "We see significant parallels with other
studies of cured hepatitis C patients.

Their formerly infected liver cells show changes in the genetic
material that influence genetic programs," explains Dr Katrin Martin,
co-lead author of the paper. This strongly suggests that the findings
now obtained in mice can be extrapolated to humans, at least in certain important respects. "One could speculate that these long-term changes
are one reason why cured hepatitis C patients have an increased risk of
liver cancer." In further studies, the researchers now aim to determine whether such changes in genetic programs also affect the cells of other
organs following temporary viral infections. At the same time, they also
want to identify the mechanism by which the body's cells manage to get
rid of viruses.

"Two questions arise from a medical perspective," concludes
Pinschewer. "How can these viruses be prevented from spreading from
cell to cell in a chronic infection and thus affecting a large number of
cells? And is it possible to reverse the changes in the genetic profile
and prevent subsequent damage?" He adds that the question of long-term
changes following a viral infection also concerns other indications,
such as asthma and long Covid.

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


========================================================================== Journal Reference:
1. Peter Reuther, Katrin Martin, Mario Kreutzfeldt, Matias Ciancaglini,
Florian Geier, Diego Calabrese, Doron Merkler, Daniel D. Pinschewer.

Persistent RNA virus infection is short-lived at the single-cell
level but leaves transcriptomic footprints. Journal of Experimental
Medicine, 2021; 218 (10) DOI: 10.1084/jem.20210408 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210824104116.htm

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