How the flu virus hacks our cells
A team has discovered how the influenza A virus hijacks the mechanism for importing iron into cells to invade its host

Date:
May 31, 2023
Source:
Universite' de Gene`ve
Summary:
Influenza epidemics, caused by influenza A or B viruses, result
in acute respiratory infection. They kill half a million people
worldwide every year. These viruses can also wreak havoc on animals,
as in the case of avian flu. A team has now identified how the
influenza A virus manages to penetrate cells to infect them. By
attaching itself to a receptor on the cell surface, it hijacks
the iron transport mechanism to start its infection cycle. By
blocking the receptor involved, the researchers were also able to
significantly reduce its ability to invade cells. These results
highlight a vulnerability that could be exploited to combat
the virus.


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FULL STORY ========================================================================== Influenza epidemics, caused by influenza A or B viruses, result in
acute respiratory infection. They kill half a million people worldwide
every year.

These viruses can also wreak havoc on animals, as in the case of avian
flu. A team from the University of Geneva (UNIGE) has identified how the influenza A virus manages to penetrate cells to infect them. By attaching itself to a receptor on the cell surface, it hijacks the iron transport mechanism to start its infection cycle. By blocking the receptor involved,
the researchers were also able to significantly reduce its ability to
invade cells. These results, published in the journal PNAS, highlight
a vulnerability that could be exploited to combat the virus.

Influenza viruses represent a major risk to human and animal health. Their potential for mutation makes them particularly elusive. ''We already
knew that the influenza A virus binds to sugar structures on the cell
surface, then rolls along the cell surface until it finds a suitable
entry point into the host cell. However, we did not know which proteins
on the host cell surface marked this entry point, and how they favoured
the entry of the virus,'' explains Mirco Schmolke, Associate Professor in
the Department of Microbiology and Molecular Medicine and in the Geneva
Centre for Inflammation Research (GCIR) at the UNIGE Faculty of Medicine,
who led this work.

A receptor as a key to infection The scientists first identified cell
surface proteins present in the vicinity of the viral haemagglutinin,
the protein used by the influenza A virus to enter the cell. One of these proteins stood out: transferrin receptor 1. This acts as a revolving
door transporting iron molecules into the cell, which are essential for
many physiological functions.

''The influenza virus takes advantage of the continuous recycling of the transferrin receptor 1 to enter the cell and infect it,'' explains Be'ryl Mazel-Sanchez, a former post-doctoral researcher in Mirco Schmolke's
laboratory and first author of this work. ''To confirm our discovery,
we genetically engineered human lung cells to remove the transferrin
receptor 1, or on the contrary to overexpress it. By deleting it in
cells normally susceptible to infection, we prevented influenza A from entering. Conversely, by overexpressing it in cells normally resistant
to infection, we made them easier to infect''.

Inhibiting this mechanism The research team then succeeded in reproducing
this mechanism by inhibiting the transferrinreceptor 1 using a chemical molecule. ''We tested it successfully on human lung cells, on human lung
tissue samples and on mice with several viral strains,'' says Be'ryl Mazel-Sanchez. ''In the presence of this inhibitor, the virus replicated
much less. However, in view of its potentially oncogenic characteristics,
this product cannot be used to treat humans.'' On the other hand,
anti-cancer therapies based on the inhibition of the transferrin receptor
are under development and could also be interesting in this context.

''Our discovery was made possible thanks to the excellent collaboration
within the Faculty of Medicine as well as with the University Hospitals
of Geneva (HUG) and the Swiss Institute of Bioinformatics (SIB),'' the
authors add. In addition to the transferrin receptor 1, scientists have identified some 30 other proteins whose role in the influenza A entry
process remains to be deciphered. It is indeed likely that the virus uses
a combination involving other receptors. ''Although we are still far
from a clinical application, blocking the transferrin receptor 1 could
become a promising strategy for treating influenza virus infections in
humans and potentially in animals."
* RELATED_TOPICS
o Health_&_Medicine
# Influenza # Bird_Flu # Cold_and_Flu # Cancer
o Plants_&_Animals
# Bird_Flu_Research # Virology # Molecular_Biology #
Biology
* RELATED_TERMS
o Avian_flu o Flu_vaccine o Pandemic o Spanish_flu o
Influenza_pandemic o H5N1 o Gastroenteritis o Virus

========================================================================== Story Source: Materials provided by Universite'_de_Gene`ve. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Beryl Mazel-Sanchez, Chengyue Niu, Nathalia Williams, Michael
Bachmann,
He'le`na Choltus, Filo Silva, Ve'ronique Serre-Beinier, Wolfram
Karenovics, Justyna Iwaszkiewicz, Vincent Zoete, Laurent Kaiser,
Oliver Hartley, Bernhard Wehrle-Haller, Mirco Schmolke. Influenza
A virus exploits transferrin receptor recycling to enter host
cells. Proceedings of the National Academy of Sciences, 2023; 120
(21) DOI: 10.1073/ pnas.2214936120 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230531102006.htm

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