EFFECT OF LOW pH ON THE HEPATITIS A VIRUS MATURATION CLEAVAGE

Cleavage of VP0 to VP2 via intramolecular scission is known as the viral maturation cleavage, as VP0 is found in immature particles, whilst VP2 is found in mature particles. The effect of low pH on the kinetics of hepatitis A virus (HAV) capsid protein VP0 cleavage in provirions was examined by Western blot analysis. VP0 scission was found to be dramatically enhanced under acidic conditions, similar to those encountered on entry of virus particles into the cell via endocytosis. The cleavage of VP0 to VP2 led to an increase in the specific infectivity of viral particles, indicating that mature virions are more infectious than immature provirions. The data are consistent with a model where conformational changes induced by low pH aid scission of VP0, and the increase in kinetics of VP0 cleavage may have relevance for viral uncoating, as only mature HAV particles are thought capable of uncoating within the host cell.