IN-VIVO TROPISM OF HEPATITIS-C VIRUS GENOMIC SEQUENCES IN HEMATOPOIETIC-CELLS - INFLUENCE OF VIRAL LOAD, VIRAL GENOTYPE, AND CELL PHENOTYPE

Extrahepatic sites capable of supporting hepatitis C virus (HCV) repli cation have been suggested. We analyzed the influence of virological f actors such as viral genotype and viral load, and cellular factors suc h as cell phenotype, on the detection rate of HCV sequences in hematop oietic cells of infected patients. Thirty-eight chronically infected p atients were included in the study: 19 infected by genotype 1 isolates (1a and 1b), 13 by nongenotype 1 isolates (including genotypes 2 a/c, 3a, and 4), and 6 coinfected by genotype 1 and 6 isolates. Polymerase chain reaction (PCR) detection efficiency of viral genomic sequences, both the positive and negative strand RNA, was evaluated using RNA tr anscripts derived from genotype 1, 2, 3, and 4 cloned sequences and fo und to be equivalent within one log unit. The serum viral load, rangin g from less than 2 x 10(5) Eq/mL to 161 x 10(5) Eq/mL, did not influen ce the detection rate of either strand of RNA in patients' peripheral blood mononuclear cells (PBMCs). Positive and negative strand RNA were found in PBMCs of all 3 cohorts of patients with a detection rate ran ging from 15% to 100% and from 8% to 83.3% for the positive and negati ve strand RNA, respectively. Coinfected patients showed a detection ra te in all cases greater than 80%. Patients infected with genotype 1 is olates showed a higher detection rate of either strands of RNA when co mpared with patients infected with other genotypes (P < .001 and P < . 04). Both strands were found restricted to polymorphonuclear leukocyte s, monocytes/macrophages, and B (but not T) lymphocytes. These data sh ow that HCV genomic sequences, possibly reflecting viral replication, can be detected in PBMCs of chronically infected patients independent of the viral load and that specific associated cell subsets are implic ated in the harboring of such sequences. (C) 1998 by The American Soci ety of Hematology.