Life cycle of influenza virus
Typically, influenza is transmitted from infected mammals
through the air by coughs or sneezes, creating aerosols containing the
virus, and from infected birds through their droppings. Influenza can
also be transmitted by saliva, nasal secretions, feces and blood.
Infections occur through contact with these bodily fluids or with
contaminated surfaces. Flu viruses can remain infectious for about
one week at human body temperature, over 30 days at 0 °C (32 °F),
and indefinitely at very low temperatures (such as lakes in northeast
Siberia). They can be inactivated easily by disinfectants and
detergents. The viruses bind to a cell through interactions between its
hemagglutinin glycoprotein and sialic acid sugars on the surfaces of
epithelial cells in the lung and throat. The cell imports the virus by
endocytosis. In the acidic endosome, part of the haemagglutinin
protein fuses the viral envelope with the vacuole's membrane,
releasing the viral RNA (vRNA) molecules, accessory proteins and
RNA-dependent RNA polymerase into the cytoplasm. These proteins
and vRNA form a complex that is transported into the cell nucleus,
where the RNA-dependent RNA transcriptase begins transcribing
complementary positive-sense cRNA. The cRNA is either exported
into the cytoplasm and translated or remains in the nucleus. Newlysynthesised viral proteins are either secreted through the Golgi
apparatus onto the cell surface (in the case of neuraminidase and
hemagglutinin) or transported back into the nucleus to bind vRNA
and form new viral genome particles . Other viral proteins have
multiple actions in the host cell, including degrading cellular mRNA
and using the released nucleotides for vRNA synthesis and also
inhibiting translation of host-cell mRNAs.
Negative-sense vRNAs that form the genomes of future viruses, RNAdependent RNA transcriptase, and other viral proteins are assembled
into a virion. Hemagglutinin and neuraminidase molecules cluster
into a bulge in the cell membrane. The vRNA and viral core proteins
leave the nucleus and enter this membrane protrusion (step 6). The
mature virus buds off from the cell in a sphere of host phospholipid
membrane, acquiring hemagglutinin and neuraminidase with this
membrane coat. As before, the viruses adhere to the cell through
hemagglutinin; the mature viruses detach once their neuraminidase
has cleaved sialic acid residues from the host cell. After the release of
new influenza virus, the host cell dies.
The separation of the genome into eight separate segments of
vRNA allows mixing (reassortment) of the genes if more than one
variety of influenza virus has infected the same cell (superinfection).
The resulting alteration in the genome segments packaged in to viral
progeny confers new behavior, sometimes the ability to infect new
host species or to overcome protective immunity of host populations
to its old genome (antigenic shift is a property of influenza virus and
results in the sudden appearance of a serotypec which has a potential
to cause a pandemic ( major antigenic changes in HA or NA ).while
the antigenic drift that occurs within a serotype such as H1N1
resulted in appearance of aviriant with minor antigenic differences
from parent strain is due to the accumulation of point mutations in
the gene resulting in amino acid changes in the protein )
Clinical Findings
Uncomplicated Influenza , Pneumonia , Reye's Syndrome
Serology
Antibodies
to
several
viral
proteins
(hemagglutinin,
neuraminidase, nucleoprotein, and matrix) are produced during
infection with influenza virus. The immune response against the HA
glycoprotein is associated with resistance to infection.
Treatment
Amantadine hydrochloride & remantadine are M2 ion
channel inhibitors for systemic use for treatment of influenza
A . The NA inhibitors zanamivir & oseltamivir were used for
treatment of influenza A & B.