Influenza virus

Influenza viruses are enveloped viruses, containing a segmented RNA genome, and are members of the family Orthomyxoviridae. Influenza viruses are divided into three types: A, B, and C. Types A and B cause most human influenza in annual winter epidemics. Influenza A viruses are further divided into subtypes based on the hemagglutinin (HA) and neuraminidase (NA) genes. The WHO nomenclature for classification of influenza strains is as follows: Type (A, B, or C)/Geographic origin/Isolate #/Year of isolation/subtype (HA and NA); e.g. A/Sydney/5/97 (H3N2). There are 16 HA subtypes and 9 NA subtypes; HA 1, 2, and 3, and NA 1 and 2 typically circulate in humans. HA is the viral protein that binds to sialic acid on host cells and is a major determinant of species tropism. The HA proteins of the types that usually circulate in humans (H1, H2 and H3) preferentially bind to the particular sialic acid moieties present on human respiratory epithelial cells. Conversely, HA in viruses that circulate in birds bind with far greater affinity to sialic acid moieties present in avian cells. The other HA and NA subtypes primarily circulate in migratory shore birds, with a few subtypes occurring naturally in horses. This provides a reservoir of novel influenza HA and NA subtypes in nature to which humans have no pre-existing immunity. The mechanisms of influenza virus replication allow for two additional sources of viral mutation, to evade host immunity or introduce completely novel subtypes. The influenza virus genome consists of segmented, single-stranded RNA molecules. The RNA polymerase enzyme that copies the genome to produce progeny virions is error-prone and, unlike DNA polymerases, has no inherent proofreading activity to correct mistakes. This leads to point mutations and progressive variation in protein sequences called 'antigenic drift'. Furthermore, viruses with segmented genomes can exchange or reassort genome segments when two different viruses infect the same cell. Reassortment leads to a complete change of the HA or NA proteins. If the new type has not circulated in humans recently, there is no pre-existing immunity in the population. The encoding of HA and NA by separate RNA molecules facilitates the reassortment of these genes in animals simultaneously infected by two different subtypes. For example, H3N1 virus has been recovered from pigs simultaneously infected with swine flu virus (H1N1) and the Hong King virus (H3N2) [6]. This abrupt change of a major immune target is called 'antigenic shift' and is a major source of pandemic strains of influenza.

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Swine Influenza

Swine Influenza

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