ABSTRACT
Influenza viruses have a segmented negative strand RNA genome, a helical nucleocapsid and a lipid envelope, and belong to the family Orthomyxoviridae. Typing (A, B and C) is on the basis of internal proteins, sub-typing (type A only) on the nature of the two external glycoproteins, hemagglutinin (HA) and neuraminidase (NA). HA binds to sialic acid residues on the surface of respiratory epithelial cells. Entry is via endocytotic vesicles, and after uncoating, viral RNA is transported to the nucleus. Virus particles leave the cell by budding. Infection is cytolytic. Transmission is via droplets released from the respiratory tract, and possibly by airborne routes. Prior to the COVID pandemic, epidemics of influenza occurred on an annual basis in the winter. Global pandemics were interspersed at irregular intervals, with considerably higher infection and mortality rates. Pandemics are thought to arise from genetic reassortment between human and avian viruses resulting in new influenza A subtypes – antigenic shift – although alternative mechanisms include direct trans-species transmission with adaptive mutations. Interpandemic epidemics arise because of Darwinian evolution of mutations in the surface HA and NA proteins – antigenic drift. Influenza viruses are potent inducers of pro-inflammatory cytokines such as interferon, which account for the often very pronounced systemic response to infection in addition to respiratory symptoms and signs. A number of influenza proteins have been shown to impede this innate immune response. Diagnosis is by genome or antigen detection in a throat swab. Mortality is highest in those with co-morbidities and the elderly. Neuraminidase inhibitors are the mainstay of therapy and are also used as prophylaxis for exposed high-risk patients. Prevention is by vaccination either with subunit vaccines containing HA and NA or live cold-adapted attenuated viruses. Annual reconsideration of vaccine content is required to cope with antigenically drifted viruses.
