Large Scale Production of Hepatitis A Virus in Cell Culture: Effect of Type of Infection on Virus Yield and Cell Integrity

Approaches to cell culture propagation of hepatitis A virus (HAV) have used either acute infection by passage of infected cell lysates or supernatants into uninfected cells or the passage of persistently infected cells. The findings presented here d monstrate that the growth and recovery of purified virus from foetal rhesus monkey kidney (FRhK4) cells persistently infected with HAV isolate HAS-15 decreased over a 2 to 3 month period. In contrast, high multiplicity acute infection of FRhK4 cells with purified HAS-15 HAV resulted in degeneration f the cell monolayer 2 to 3 weeks later. Large scale propagation of acutely infected cells followed by traditional picornavirus purification procedures reproducibly yielded milligram amounts of purified virus. Conditions for the growth of hepatitis A virus (HAV) in various cell lines and under various conditions have been described in numerous reports (Provost & Hilleman, 1979; Flehmig, 1980