Hep C: Mystery of how deadly virus hides in humans is solved

Date:
July 5, 2023
Source:
University of Copenhagen - Faculty of Science
Summary:
With a new method for examining virus samples researchers have
solved an old riddle about how Hepatitis C virus avoids the human
body's immune defenses. The result may have an impact on how we
track and treat viral diseases in general.


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FULL STORY ==========================================================================
With a new method for examining virus samples researchers from the
University of Copenhagen have solved an old riddle about how Hepatitis
C virus avoids the human body's immune defenses. The result may have an
impact on how we track and treat viral diseases in general.

An estimated 50 million people worldwide are infected with with chronic hepatitis C. The hepatitis C virus can cause inflammation and scarring of
the liver, and in the worst case, liver cancer. Hepatitis C was discovered
in 1989 and is one of the most studied viruses on the planet. Yet for
decades, how it manages to evade the human immune system and spread
through the body has been a riddle -- one that Danish researchers have
become the first to solve.

A new method for examining virus samples has led researchers at the
University of Copenhagen and Hvidovre Hospital to the answer, which is:
the virus just puts on a 'mask'.

By donning a mask, the virus can remain hidden while making copies of
itself to infect new cells. The mask cloaks the virus in the form of a
molecule already in our cells. Disguised by the molecule, our immune
systems confuse the virus with something harmless that needn't be
reacted to.

"How the Hepatitis C virus manages to hide in our liver cells
without being detected by the immune system has always been a bit of a
mystery. Our revelation of the virus' masking strategy is important, as
it could pave the way for new ways of treating viral infections. And it
is likely that other types of viruses use the same trick," says Associate Professor Jeppe Vinther of the Department of Biology, who together with associate professor Troels Scheel and professor Jens Bukh from Copenhagen Hepatitis C Program headed the research.

Camouflage for a malicious virus The mask used by the hepatitis virus to
hide in our cells is called FAD, a molecule composed of Vitamin B2 and
the energy carrying molecule ATP. FAD is vital for our cells to convert
energy. The FAD molecule's importance and familiarity to our cells makes
it ideal camouflage for a malicious virus.

For several years, the research team had a good idea that FAD was helping
the virus hide in infected cells, but they lacked a clear way to prove
it. To solve the challenge, they turned to Arabidopsis, a well-known experimental plant among researchers.

"We were getting desperate to find a way to prove our hypothesis, which
is when we purified an enzyme from the Arabidopsis plant that can split
the FAD molecule in two," explains Anna Sherwood from Department of
Biology, who together with Lizandro Rene Rivera Rangel are first authors
of the study.

Using the enzyme, the researchers were able to split the FAD and prove
that the hepatitis C virus used it as a mask.

Other viruses probably use the same trick Like both the coronavirus
and influenza virus, Hepatitis C is an RNA virus. Its genetic material
consists of RNA that must be copied once the virus enters its host
organism. New RNA copies are used to take over new cells, and one end
of the RNA's genetic material is masked by the FAD.

According to Jeppe Vinther, it is very realistic that other RNA viruses
use similar masking techniques to spread without being detected by
cellular control systems. In fact, researchers have already found another
virus that uses the same strategy. And there are likely more.

"All RNA viruses have the same need to hide from the immune system and
there is a good chance that this is just the beginning. Now that we're
attuned to this trick, it opens up the possibility of developing new
and perhaps improved methods of tracking and treating viral infections
in the future," concludes Jeppe Vinther.

The research is funded by Independent Research Fund Denmark, as well
as several other Danish and European foundations and conducted in a collaboration between Jeppe Vinther's research group at the Department
of Biology, University of Copenhagen, and Troels Scheel and Jens Bukh's research groups from the Copenhagen Hepatitis C Program, which are located
at UCPH's Department of Immunology and Microbiology and the Department
of Infectious Diseases at Hvidovre Hospital.

* RELATED_TOPICS
o Health_&_Medicine
# Viruses # Liver_Disease # Infectious_Diseases #
HIV_and_AIDS
o Plants_&_Animals
# Virology # Microbes_and_More # Biology # Microbiology
* RELATED_TERMS
o Hepatitis_E o HIV o Chickenpox o Natural_killer_cell o
Epstein-Barr_virus o Pandemic o Rubella o Chemotherapy

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========================================================================== Journal Reference:
1. Sherwood, A.V., Rivera-Rangel, L.R., Ryberg, L.A. et al. Hepatitis C
virus RNA is 5'-capped with flavin adenine dinucleotide. Nature,
2023 DOI: 10.1038/s41586-023-06301-3 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/07/230705115127.htm

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