• Immunologists unravel battle plans of de

    From ScienceDaily@1:317/3 to All on Tue Apr 12 22:30:42 2022
    Immunologists unravel battle plans of deadly coronaviruses

    Date:
    April 12, 2022
    Source:
    Trinity College Dublin
    Summary:
    Researchers have unraveled new secrets behind coronaviruses'
    battle plans -- providing new insights into how these deadly
    viruses sometimes win the war against human immune systems. The
    immunologists have discovered how SARS and MERS proteins block the
    induction of antiviral proteins, which prevents us from mounting
    a strong innate immune response against infection.



    FULL STORY ========================================================================== Immunologists from Trinity College Dublin, who have worked on
    coronaviruses for the past decade, have just unravelled new secrets
    behind the viruses' battle plans -- providing new insights into how
    these deadly viruses sometimes win the war against human immune systems.


    ==========================================================================
    The immunologists, led by Dr Nigel Stevenson, Assistant Professor in Viral Immunology at Trinity, have discovered how SARS and MERS proteins block
    the induction of antiviral proteins, which prevents us from mounting a
    strong innate immune response against infection.

    The coronaviruses SARS and MERS emerged in 2002 and 2012,
    respectively. Both had higher fatality rates than COVID-19 (around 10%
    and 40%, respectively), but both infected far fewer people (around 10,000
    and 3,000, respectively).

    Although different, these two coronaviruses bear many similarities to
    SARS-COV- 2 (COVID-19), and thus drawing up blueprints of their battle
    plans provides insights with the potential to provide new therapeutic
    options for treating COVID-19 and future deadly coronaviruses that have
    yet to emerge.

    Dr Stevenson and his team discovered that SARS and MERS viruses have
    proteins that essentially throw a spanner in the works of the Interferon antiviral pathway, which -- under normal circumstances -- activates a
    cascade of responses in human cells, to produce hundreds of antiviral
    proteins that block viral replication.

    Dr Nigel Stevenson, Head of the Viral Immunology team in the School
    of Biochemistry and Immunology, is based in the Trinity Biomedical
    Sciences Institute (TBSI). He is the senior author of a 2022 research
    article, which has just been published in the Journal, Viruses. He said:
    "Over time, humans have evolved to fight viral infections by producing molecules called Interferons. When a virus is encountered Interferons
    are produced, which, in turn, activates an antiviral pathway in our
    cells that is at the heart of our immediate immune response. The pathway produces specific proteins that switch hundreds of our anti-viral genes
    on. These genes then produce lots of different antiviral proteins that
    attack -- and in most cases - - kill the virus. In doing so, Interferons 'interfere' with a virus' life cycle."


    ========================================================================== "However, viruses have also evolved over time to suppress and avoid our
    immune system responses. And our research aims to understand how viruses suppress the response to Interferons. Our current research has discovered
    that SARS and MERS prevent key proteins from being activated and entering
    the nucleus in our cells. The nucleus is where our DNA is stored and
    where genes are switched on, to generate a proper immune response.

    "The hope is that if we can design new drugs to inhibit the ability
    of coronaviruses to suppress the Interferon pathway, we should be
    able to treat people far more effectively. And given the similarity in coronaviruses and their modes of action, such a drug would likely prove effective against all the deadly coronaviruses." Dr Stevenson added: "Therapeutic Interferon is a drug used to fight certain infections,
    but it has never proved very effective against coronaviruses. Now we
    think we know why - - if the Interferon pathway is essentially disabled,
    it can't stimulate a response.

    "If we could restore the natural ability of our immune systems to fight
    viral infection and prevent viral replication, we could treat infected
    people with much greater success. In addition, if we could develop a therapeutic that stop viruses from destroying the Interferon pathway,
    it would in theory open the door to directly attacking the virus."
    First author on the research article is Yamei Zhang, who previously
    spent research time with Dr Stevenson's collaborators in Hong Kong
    University. She and Dr Stevenson were working on this research before SARS-CoV-2 emerged and the COVID-19 pandemic developed.

    The work was funded by Science Foundation Ireland and the China
    Scholarship Council. A copy of the journal article is available on
    request.


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


    ========================================================================== Journal Reference:
    1. Yamei Zhang, Siobhan Gargan, Fiona M. Roche, Matthew Frieman,
    Nigel J.

    Stevenson. Inhibition of the IFN-a JAK/STAT Pathway by MERS-CoV
    and SARS- CoV-1 Proteins in Human Epithelial Cells. Viruses, 2022;
    14 (4): 667 DOI: 10.3390/v14040667 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220412140912.htm

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