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.