Hepatitis A virus: growth characteristics of in vivo and in vitro propagated wild and attenuated virus strains.

ABSTRACT

Serial passage of the MS-1 strain hepatitis A virus (HAV) in marmosets was shown to increase the yield of virus and to shorten the incubation period from approximately 55 days in the first passage to 3-7 days in the ninth and higher passages. Intravenous inoculation of susceptible chimpanzees with MS-1 HAV was found to result in a typical course of disease in two animals who had received eighth marmoset-passage virus, including the occurrence of elevated ALT activity, presence of HAV antigen in liver and stool, and seroconversion to anti-HAV. Two chimpanzees inoculated with 20th passage MS-1 HAV (M001 liver homogenate) exhibited normal or nearly normal ALT activity and had no demonstrable or significant HAV in weekly liver biopsy specimens or in serial stool suspensions obtained during 64 days of observation. However, both animals seroconverted to anti-HAV within 2 weeks after inoculation, as did the animals who had received eighth passage MS-1 HAV. These findings suggest that subpassage of the MS-1 strain of HAV in marmosets resulted in the generation of an attenuated virus strain that was still capable of inducing a vigorous antibody response in intravenously infected chimpanzees. Serial propagation of wild and attenuated strains of HAV (HAS-15 and MS-1/M001, respectively) in FRhK-4 cells was associated with a significant decrease in the growth period for both viruses. Our studies have also shown that HAS-15 HAV can be recovered in maximum yield in later passages as early as 2 to 3 days after inoculation.