SEQUENCE-ANALYSIS OF THE HEPATITIS-C VIRUS GENOME RECOVERED FROM SERUM, LIVER, AND PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF INFECTED CHIMPANZEES

Of 13 different strains of hepatitis C virus (HCV) in the inoculum use d, only 1 persisted in human lymphocyte cell lines infected in vitro ( N. Nakajima, M. Hijikata, H. Yoshikura, and Y. K. Shimizu, J. Virol. 7 0:3325-3329, 1996). To determine whether that particular strain (desig nated H1-2) has a tropism for lymphocytes in vivo, we sequenced hyperv ariable region 1 (HVR1) of the genome of HCV recovered from the sera, livers, and peripheral blood mononuclear cells (PBMC) of chimpanzees i nfected with plasma H77, the same inoculum used for the in vitro studi es, In the PBMC collected from two chimpanzees during the early phase of infection, H1-2 was detected as the only or predominant HVR1 sequen ce, H1-2 was also detected in PBMC obtained during persistent infectio n from a chimpanzee that had been treated with immunosuppressants, Fro m the livers of these chimpanzees, two to six different strains were r ecovered but H1-2 was not detected. Thus, H1-2 appeared to have an aff inity for lymphocytes not only in vitro but also in vivo. In samples c ollected from a chimpanzee after 6 years of infection, however, such t issue compartmentalization of the HCV genome was not observed; a singl e strain became predominant in the serum, liver, and PBMC. An HCV stra in capable of replicating in both the liver and PBMC probably emerged during in vivo replication and persisted.