Pathogenesis of the H5N1 Avian Influenza Virus in Humans and Mammalian Models

Abstract

H5N1 avian influenza virus is a highly virulent virus. In many avian as well as mammalian species, the virus causes severe disseminated diseases with an almost 100% fatality rate. The reason for this extremely high virulence is not yet well understood. Highly cleavable hamagglutinin allowing the virus to disseminate outside respiratory and digestive tracts is believed to be a major virulence factor. Apoptosis induction by viral protein PB1-F2 and hyperinduction of proinflammatory cytokines may also contribute to virulence. In humans, although viral RNA could be detected in a number of organs, severe inflammation and tissue damage were only observed in the human lungs, and viral antigen was only observed in the type II alveolar epithelial cells. Apoptosis of these cells may play a critical role in respiratory failure, which is the major cause of death. Although high mortality has been shown to be associated with a high viral load, mortality remains high even in the presence of antiviral therapy. This suggests that some damage may not be caused directly by viral replication. A better understanding of viral pathogenesis may lead to a better treatment of this deadly infection.