Structure and Function of Influenza Virus
HemagglutininAntigenic
Drift and Shift of HA
by Gary C. Port
Influenza Virus
Influenza A virus is divided into subtypes based on the antigenic nature of their
hemagglutinin and neuraminidase glycoproteins. The emergence of new
pandemic strains of
influenza A virus results from the appearance of a new virus subtype containing a
novel hemagglutinin (HA) and/or neuraminidase (NA) immunologically distinct from those of
the previously circulating strain.
Antigenic Drift
Antigenic Drift occurs as minor changes in HA and NA accumulate amino acid substitutions
due to random mutations. Five antigenic sites
have mapped on HA, and antibodies to these sights
neurtalize the infectivity of the virus. The region of antigenic variation that occurs
during drift covers the surface of the globular head, especially around the
receptor-binding pocket. This variation allows the conserved amino acids responsible for
sialic acid binding to remain constant, while allowing the virus to avoid neurtalization
by antibodies.
Antigenic Shift
Antigenic Shift occurs when an entirely novel HA and/or NA emerge. The appearance
of swine influenza occured in 1918. The HA was found to be related to swine influenza
virus and was called H1. The "Spanish Flu" of 1918 traveled the globe in 4
months, killing more than 20 million people (1% of the world population) causing the most
lethal epidemic in human history. This strain circulated until 1957, when H2N2 (Asian
Strain) was isolated. H2 was shown to have no cross reactivity with H1. This spread and
changed until the next pandemic of 1968 with the introduction of a new HA subtype called
H3 (Hong Kong). These drastic changes came from reassortment of Human viruses and
influenza viruses of animal origin. Since influenza virus is a segmented virus, it is not
difficult for the HA gene of say a human virus to get swapped with the HA gene of any
other animal influenza virus.
Recently the story has once again
brought us back to Hong Kong. An Influenza strain found in chickens (with an H5
hemagglutinin) has been shown to infect and be very lethal to humans (33% mortality) since
we have no defense against it. The virus currently can only be transmitted from chicken to
human and not human to human, but estimates have been made that if this strain of chicken
influenza recombines with human influenza allowing human to human transmission, another
pandemic could arise killing 60 million people. Currently, the FDA Vaccine Advisory Panel
is working on developing a vaccine against H5 to try to avoid another deadly pandemic.