Virulence of influenza A virus for mouse lung.

The experimental infection of mouse lung with influenza A virus has proven to be an invaluable model for studying the mechanisms of viral adaptation and virulence. These investigations have identified critical roles for the haemagglutinin (HA) and matrix (M) genes of the virus in determining virulence for mouse lung. For the HA gene, the loss of glycosylation sites from the encoded polypeptide or changes which may affect the pH of HA-mediated endosome fusion have been observed following adaptation. These alterations also have the potential to impact on receptor specificity, beta inhibitor sensitivity and activation cleavage which may act in concert to account for the increased virulence of adapted strains. For the M gene, two specific changes in the M1 protein have been identified in strains adapted to, or virulent for, mouse lung. These changes are likely to affect pH-dependent association/dissociation of M1 with the viral ribonucleoprotein, and control virulence as well as growth. The role of other genes in mouse lung virulence remains unknown.