HEPATITIS-C VIRUS QUASI-SPECIES IN PATIENTS INFECTED WITH HIV-1 - CORRELATION WITH EXTRAHEPATIC VIRAL REPLICATION

Hepatitis C virus (HCV) sequences recovered from serum, peripheral blo od mononuclear cells (PBMCs), and various tissues from human immunodef iciency virus type 1 (HIV-l) positive patients were compared by single strand conformational polymorphism (SSCP) and sequencing. In five pat ients, paired serum and PBMCs samples were analyzed while in two other patients multiple autopsy tissues were studied. Sequences amplified f rom the NS5 and E2 regions were consistently identical in the same pat ient; however, three PBMCs samples and three different tissue samples (pancreas and adrenal gland in one patient and lymph node in the other patient) contained 5' untranslated region (5' UTR) sequences that wer e different from circulating sequences. The presence of 5' UTR sequenc es differing from circulating sequences correlated with the presence o f HCV RNA negative strand, as the latter was detected by a Tth-based s trand-specific assay in all but one of these samples. These two indepe ndent lines of evidence: viral sequence differences and the presence o f RNA negative strand in the same tissues strongly argue for the genui ne presence of extrahepatic HCV replication, at least in the setting o f HIV-1 infection. (C) 1998 Academic Press.