Selective transmission of hepatitis C virus genotypes and quasispecies in humans and experimentally infected chimpanzees.
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.
Nainan
Omana V
OV
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.
Lu
Ling
L
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.
Gao
Feng-Xiang
FX
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.
Meeks
Emory
E
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.
Robertson
Betty H
BH
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.
Margolis
Harold S
HS
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.
D000818:Animals; D004195:Disease Models, Animal; D005169:Factor VIII / Q000008:administration & dosage*; D005838:Genotype; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000635:transmission* / Q000821:virology; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D065227:Transfusion Reaction; D014759:Viral Envelope Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism
D014759:Viral Envelope Proteins; D005169:Factor VIII