Pathogens and disease
Influenza viruses belong to the family Orthomyxoviridiae, which is characterized by a single-stranded and segmented RNA genome. The influenza viruses are classified into types A, B and C on the basis of their core proteins, whereas the subtypes of influenza A viruses are determined by envelope glycoproteins possessing either haemagglutinin (HA) or neuraminidase (NA) activity. High mutation rates and frequent genetic reassortments of these viruses contribute to great variability of the HA and NA antigens. Minor point mutations causing small changes ("antigenic drift") occur relatively often. Antigenic drift enables the virus to evade immune recognition, resulting in repeated influenza outbreaks during interpandemic years. Major changes in the HA antigen ("antigenic shift") are caused by reassortment of genetic material from different A subtypes. Antigenic shifts resulting in new pandemic strains are rate events, occurring through reassortment between animal and human subtypes, for example in co-infected pigs. Type B virus does not exhibit antigenic shirts and is not divided into subtypes.
Influenza A viruses infect a range of mammalian (e.g. pigs and horses) and avian species, whereas type B and C infections are largely restricted to humans. Only types A and B cause human disease of any concern. All of the currently identified 16 HA and 9 NA subtypes of influenza A viruses are maintained in wild, aquatic bird populations. Humans are generally infected by viruses of the subtypes H1, H2 or H3, and N1 or N2. Animal subtypes of influenza viruses are usually not very efficient in infecting humans without previous adaptation to mammalian hosts or reassortment with human viruses. When animal subtypes occasionally cause human illness directly, fatality rates may be high. For example, in 1997 the avian H5N1 outbreak in Hong Kong SAR caused 18 confirmed human cases, 6 of which were fatal. The H5N1 virus has undergone subsequent antigenic and genetic changes, and in recent years, highly pathogenic H5N1 strains have caused large poultry outbreaks in a number of Asian countries. In addition, other avian subtypes such as H9N2, H7N7, H7N3 and H10N7 have recently caused outbreaks in birds and occasionally human disease in various parts of the world. Should avian-human reassortants or mutants such as the highly pathogenic H5N1 strains acquire the capacity to transmit effectively among humans, the outcome could be disastrous.