HEPATITIS-A VIRUS - GROWTH-CHARACTERISTICS OF INVIVO AND INVITRO PROPAGATED WILD AND ATTENUATED VIRUS-STRAINS

Serial passage of the MS-1 strain hepatitis A virus (HAV) in marmosets increased the yield of virus and shortened the incubation period from .apprx. 55 days in the 1st passage to 3-7 days in the .gtoreq. 9th passages. Inoculation i.v. of susceptible chimpanzees with MS-1 HAV resulted in a typical course of disease in 2 animals who had received 8th marmoset-passage virus, including the occurrence of elevated alanine transaminase (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 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 wk after inoculation as did the animals who had received 8th passage MS-1 HAV. Thus, 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 i.v. 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. HAS-15 HAV can be recovered in maximum yield in later passages as early as 2-3 days after inoculation.