Saturday, November 22, 2014

How the Influenza A Virus Enters the Host Cell

Influenza A Virus (IAV) has, of course, major implications in regards to public health.  Given the possibility of an influenza pandemic, it is vitally important to understand the mechanism of infection for this virus, since all viruses are unique in this regard. 

IAV is a single-stranded RNA virus that is subdivided into eight RNA molecules.  Each of these is precisely packaged into helical ribonucleoproteins (vRNPs).   These vRNPs carry a copy of a viral polymerase enzyme complex and the nucleoprotein (NP).   Within the structure of the virus, these vRNPs are arranged into a capsid-like complex that forms a shell around the vRNPs.   This is the state of the virus prior to its entry into the host cell.

As IAV gains entry into the host cell, it begins a process of uncoating initiated by the acidic conditions within the endosome – a membrane-bound structure providing transport within eukaryotic cells.  In the later stages of the process, the protein hemagglutunin (HA) – native to the virus – is activated and the IAV finally is transferred to the cell cytosol – cytoplasm .  Ultimately, the vRNPs gain access to the nucleus through the nuclear membrane.  It is at this final stage that the viral genome begins to co-opt the host cellular machinery to make more copies of the virus leading to the death of the host cell and the release of many more infectious agents into the surrounding tissue.
Dr. Indranil Banerjee and his colleagues at the Institute of Biochemistry, Eidgenossische Technische Hochschule in Zurich, Switzerland studied the process of capsid disassembly in detail, since it plays such a crucial role in IAV entry into the host cell.  They found that the virus exploits the host cell’s aggresome formation and disassembly mechanisms.  An aggresome is a cellular complex that is created in response to cell stress characterized by misfolded or unfolded proteins .

By helping to elucidate the underlying mechanisms responsible for host cell entry of IAV, this knowledge creates opportunities for the application of novel therapeutic approaches to combat infection.    

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