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Selective transmission of hepatitis C virus genotypes and quasispecies in humans and experimentally infected chimpanzees

Omana V. Nainan

Ling Lu

Harold S. Margolis

Division of Viral Hepatitis, National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC), 1600 Clifton Road NE, MS A33, Atlanta, GA 30333, USA

Correspondence
Feng-Xiang Gao
Fgao{at}cdc.gov

This study determined whether selective transmission of hepatitis C virus (HCV) species occurred among human and chimpanzee recipients of contaminated blood products or plasma containing multiple genotypes, subgenotypes and quasispecies. Commercially prepared factor VIII concentrate (lot DO56), produced prior to HCV testing and inactivation, was subsequently found by direct cloning to contain the following subgenotypes: 1a and 1b (73 % of clones), 2a (13 % of clones), 2b (11 % of clones) and 3a (4 % of clones). A patient transfused with factor VIII concentrate DO56 was diagnosed with clinical non-A, non-B hepatitis and subsequently found to be infected with HCV subgenotype 1b. Among five chimpanzees inoculated experimentally with the same factor VIII concentrate, two were infected only with HCV subgenotype 1a and three were infected with approximately equivalent clonal proportions of subgenotypes 1a and 1b. HCV hypervariable region 1 (HVR1) quasispecies analysis of the DO56 factor VIII concentrate and a serum specimen from the single chimpanzee that developed a chronic HCV infection following inoculation with DO56 showed 0–56 % nucleotide variation. However, specimens from chimpanzees infected in the second to fourth passages of the DO56 inoculum had 0–8 % HVR1 quasispecies nucleotide variation. The high HVR1 quasispecies variation in the factor VIII concentrate and its first passage in chimpanzees indicates the presence of multiple HCV isolates, whereas the low variation in the second to fourth chimpanzee passages suggests transmission of a single HCV isolate. These findings strongly suggest selective transmission of HCV isolates during experimental chimpanzee infection and among humans exposed to multiple HCV species.

The GenBank/EMBL/DDBJ accession numbers for the sequence data reported here are DQ249472–DQ249796.

Deceased 3 September 2005.

Present address: Division of Gastroenterology/Hepatology, Department of Medicine, University of Kansas Medical Center, 4035 Delp, Kansas City, KS 66160, USA.

Present address: International Vaccine Institute, Kwanak PO Box 14, Seoul 151-600, Korea.

This article has been cited by other articles:

				F. Gao, O. V. Nainan, Y. Khudyakov, J. Li, Y. Hong, A. C. Gonzales, J. Spelbring, and H. S. Margolis Recombinant hepatitis C virus in experimentally infected chimpanzees J. Gen. Virol., January 1, 2007; 88(1): 143 - 147. [Abstract] [Full Text] [PDF]