The pathogenesis of influenza in humans.

The rapid evolution of influenza A and B viruses contributes to annual influenza epidemics in humans. In addition, pandemics of influenza are also caused by influenza A viruses, whereas influenza B does not have the potential to cause pandemics because there is no animal reservoir of the virus. Study of the genetic differences between influenza A and influenza B viruses, which are restricted to humans, may be informative in understanding the factors that govern mammalian adaptation of influenza A viruses. Aquatic birds provide the natural reservoir for influenza A viruses, but in general, avian influenza is asymptomatic in feral birds. Occasionally, however, highly pathogenic strains of influenza cause serious systemic infections in domestic poultry. The pathogenicity of these strains is related to the presence of a polybasic cleavage sequence in the precursor of the surface glycoprotein haemagglutinin, which makes the glycoprotein susceptible to activation by ubiquitous proteases such as furin and PC6. However, the mechanism of pathogenicity may differ in highly pathogenic strains of human influenza, such as the H1N1 pandemic strain of 1918 and the H5N1 strain involved in the outbreak in Hong Kong in 1997. Binding of host proteases by the viral neuraminidase to assist activation of the haemagglutinin, shortening of the neuraminidase and substitutions in the polymerase gene, PB2, have all been suggested as alternative molecular correlates of pathogenicity of human influenza viruses. Additionally, systemic spread in humans of pathogenic subtypes has not been demonstrated and host factors such as interferons may be crucial in preventing the spread of the virus outside the respiratory tract. Copyright 2001 John Wiley & Sons, Ltd.