Patients coinfected with the hepatitis C virus (HCV)
The prevalence of the hepatitis C virus (HCV) in paand the human immunodeficiency virus (HIV) were tients with concurrent human immunodeficiency virus studied with regard to nucleotide sequence variability (HIV) infection is higher than in the general population in the E2/NS1 first hypervariable region of the HCV gewithout HIV infection. 1,2 Interferon (IFN) treatment of nome. The nucleotide variability within individual pachronic HCV infection has not been well studied in tients was compared to patients infected only with HCV. this subgroup, but limited information suggests that The proportion of predicted synonymous and nonsynonresponse rates may be lower in patients with HCV/HIV ymous amino acid changes, and the relationship to putacoinfection than for patients with HCV infection alone. 3 tive high-antigenicity sites, were evaluated in the hyper-Furthermore, HCV-RNA titers appear to be quite varivariable envelope domain. Ninety-one clones from 10 able in patients with HCV/HIV coinfection. 4 We have patients with HCV/HIV coinfection were sequenced, following polymerase chain reaction (PCR) amplification postulated that genomic variability in the hypervariof the hypervariable region. The control HCV group inable envelope coding region could be responsible for cluded 53 clones from 7 patients. Sequence analysis entiter variation and poor interferon (IFN) responcompassed the region coding for amino acids 384 to 414. siveness in this cohort. Indeed, the immunosuppressed Consensus sequences from each patient were used as environment may allow a greater expression of varithe internal standard for nonsynonymous amino acid ability by the failure of the host to produce antibodies codon variability. Cumulative proportional comparison to antigenic variants as they emerge.
at each amino acid site revealed increased variability
The HCV genome can be classified into multiple in HCV RNA from patients with HCV/HIV coinfection types and subtypes based on the degree of homology versus HCV alone (P Γ΅ .05). The greatest variability was with consensus sequences. The genotypic characterizaobserved at amino acids 386, 397, 400, 402, 405, 407, and 414, with ΓΊ10% clonal variation at these sites. Jameson-tion tends to be stable throughout the genome, except Wolf plots were used to predict putative high-antigenicin two hypervariable regions within the putative enveity domains. Nonsynonymous clonal variation resulted lope coding region. 5 In these areas, there is a high dein alteration of putative antigenic sites within the hypergree of genomic variability. This variability may reprevariable region. All clones had at least one high-probasent the short-term mutability of the virus associated bility site. Clones with unique predicted antigenic dowith antigenic selection. 6 mains were observed more frequently in HIV/HCV
The first hypervariable domain resides at amino coinfected patients, and, independent of viral titer, were acids 384 to 414 in the genomic region designated as consistent with increased sequence variability. These the putative envelope glycoprotein (E2). Within this data suggest an accumulation of envelope variants in region, at least one immunodominant coding region has the HCV/HIV coinfected patients, which could be related to ineffective viral clearance, and may help explain prior been identified. The alteration of the amino acid sereports of interferon (IFN) resistance in this patient quence in this region was associated with a second epigroup. (HEPATOLOGY 1996;23:688-694.) sode of hepatitis in a patient. Antibodies directed against the peptide observed during the first hepatitis event did not recognize the altered peptide observed in a second episode of hepatitis. 7 The degree of variability Abbreviations: HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN, interferon; PCR, polymerase chain reaction; cDNA, complementary in the E2/NS1 hypervariable regions has been associ-DNA.