Abstract
Hepatitis C virus (HCV) causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU) infected by human immunodeficiency virus type 1 (HIV-1) are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1) gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance.
Highlights
Hepatitis C virus (HCV) infects more than 170 million individuals worldwide and is a major public health problem
A total of 138 Caucasian patients were enrolled between February and December 2008, comprising 22 cases (20 men) and 116 controls (93 men). They were all followed in four Parisian clinical centers managing patients infected with human immunodeficiency virus type 1 (HIV-1)
The overall seroprevalence of HCV in human immunodeficiency virus (HIV)-infected patients is around 24% [23], but it can reach 92.8% in HIV-1-infected intravenous drug users (IDU) (2)
Summary
Hepatitis C virus (HCV) infects more than 170 million individuals worldwide and is a major public health problem. HCV infection becomes persistent in 75% of cases. Chronic carriers frequently develop fibrosis, cirrhosis and, in some cases, hepatocellular carcinoma, especially if untreated. Because human immunodeficiency virus (HIV) and HCV share common routes of infection, coinfection with HCV is frequent among HIV-1-infected patients: in Europe, about one-third of all HIV-1-infected individuals have anti-HCV antibodies [1, 2]. The seroprevalence of HCV among HIV-1-infected individuals in France ranges from 8% when HIV-1 is transmitted via heterosexual contact to 41.7% among hemophiliacs and/or transfusion recipients and more than 92% among intravenous drug users (IDU) [3]. Individuals who acquired HIV-1 via intravenous drug use but remain uninfected by HCV are rare
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