Identification of Variants of Hepatitis C Virus (HCV) Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

Identification of Variants of Hepatitis C Virus (HCV) Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

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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 COCONUT 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 FAST ARTHRITIS PAIN 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.