RNA-dependent cleavage of VP0 capsid protein in provirions of hepatitis A virus.

Stable provirions of hepatitis A virus containing up to 62% VP0 were purified from infected BS-C-1 cells by sucrose density gradient ultracentrifugation, and conversion of these provirions to virions through maturation cleavage of VP0 capsid protein was demonstrated. VP0 cleavage was slow but linear over 7 days at 37 degrees, with mature virions containing between 3 and 7 copies of VP0 in separate experiments. Cleavage of approximately 25% of VP0 molecules (15 copies) was accompanied by a twofold increase in specific infectivity. Particles with reduced levels of VP0 were observed to sediment more rapidly in sucrose than VP0-rich provirions, reflecting conformational changes in the particles. The kinetics and temperature-dependence of VP0 cleavage further suggest that such conformational changes accompanying VP0 cleavage are necessary for the formation of subsequent catalytic sites.