SUPERINFECTION OF CHIMPANZEES CARRYING HEPATITIS-C VIRUS OF GENOTYPE II 1B WITH THAT OF GENOTYPE III/2A OR I/1A/

Three chimpanzees persistently infected with hepatitis C virus of geno type II/1b were challenged with hepatitis C virus of genotype III/2a a nd 6 wk later with hepatitis C virus of genotype I/1a. They were teste d for titers of total and genotype-specific hepatitis C virus RNA, as well as for serum transaminase levels, until 52 wk after the first cha llenge. One chimpanzee (CH489) with intermittent low hepatitis C virus RNA titers of genotype II/1b in serum was superinfected with hepatiti s C virus of genotype III/2a between wk 1 and 7 after the challenge; s uperinfection was accompanied by fluctuating high transaminase levels. Later, the animal was superinfected with hepatitis C virus of genotyp e I/1a. Superinfection was accompanied by persistently high transamina se levels immediately after the challenge. Hepatitis C virus of genoty pe I/1a persisted, whereas hepatitis C virus of genotype II/1b was und etectable 22 wk after the challenge and thereafter. In another chimpan zee (CH353) with intermittent low hepatitis C virus RNA titers of geno type II/1b, hepatitis C virus of genotype III/2a induced fluctuating h igh levels of serum transaminases without revealing itself in serum. T hen, HCV of genotype I/1a superinfected her, induced persistently high transaminase levels and took over HCV of genotype II/1b at 22 wk afte r the challenge and thereafter. The third chimpanzee (CH451) with pers istently high HCV RNA titers of genotype II/1b did not reveal HCV RNA of genotype III/2a in serum after the challenge, although transaminase s sharply increased. Low-titered HCV RNA of genotype I/1a was detected at 18 wk after the challenge. He continued to have elevated transamin ase levels and high-titered HCV RNA of genotype II/1b throughout the o bservation period. These results indicate superinfection with HCV of d ifferent genotypes in chimpanzees, newly introduced HCV replacing or b eing expelled by the predecessor HCV with each infection inducing an e pisode of liver injury.