A Critical Role of Cell Tropism for the Pathogenesis of Influenza

Influenza A virus, together with Influenza B virus, Influenza C virus, Isavirus and Thogotovirus, are the five genera forming the family Orthomyxoviridae. Orthomyxoviridae are enveloped, negative-stranded RNA viruses with a segmented genome. Influenza A viruses can be further categorized into subtypes based on two surface glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA). To date, 16 different HAs and 9 different NAs have been found and may occur in virtually all possible combinations. Free-ranging waterbirds are considered to be the natural reservoir of all influenza A viruses. Even though some mammalian species— humans, pigs, horses and dogs—harbor their own influenza A viruses, there is strong evidence that these mammalian viruses originate from avian influenza A viruses. In addition, avian influenza A viruses may cross the species barrier to other mammals without developing into a stable lineage in the new host species. An example is the outbreak of avian influenza virus of the subtype H7N7 in harbor seals in 1979. Interestingly, the primary replication site for influenza A virus differs between birds and mammals. In birds, the virus replicates primarily in the intestinal tract, whereas in mammals, it replicates primarily in the respiratory tract. An important feature of avian influenza viruses is their capacity to mutate into forms that cause high mortality in poultry. Such mutations only have been recorded for the subtypes H5 and H7 and occur after transmission of these viruses to poultry. Based on their capacity to cause morbidity and mortality in chickens, avian influenza viruses are classified as low pathogenic avian influenza virus (LPAIV) or high pathogenic avian influenza virus (HPAIV).

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