title: Identification of Variants of Hepatitis C Virus (HCV) Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.
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.
authors.affiliation: Univ Paris Sud, Faculté de Médecine, Hôpitaux Universitaires Paris Sud, Hopital Bicetre, 94275, Le Kremlin-Bicêtre, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Fouquet
authors.affiliation: APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaire Paris Centre, Hôpital Hôtel Dieu, Paris, France.|Université Paris Descartes, EA 7327, Faculté de Médecine site Necker, Sorbonne Paris Cité, Paris, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.affiliation: APHP, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Hôpital Bicêtre, 94275, Le Kremlin-Bicêtre, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Quertainmont
authors.affiliation: APHP, Service de Médecine Interne, Hôpitaux Universitaires Paris Centre, Hôpital Cochin, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.affiliation: APHP, Service des Maladies Infectieuses et Tropicales, Hôpitaux Universitaires Paris Nord val de Seine, Hospitalier Bichat-Claude Bernard, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rioux
authors.affiliation: Centre Médical de l'Institut Pasteur, 75015, Paris, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Duvivier
authors.affiliation: APHP, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Hôpital Bicêtre, 94275, Le Kremlin-Bicêtre, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.affiliation: Univ Paris Sud, Faculté de Médecine, Hôpitaux Universitaires Paris Sud, Hopital Bicetre, 94275, Le Kremlin-Bicêtre, France.
authors.forename: Micheline
authors.initials: M
authors.lastname: Misrahi
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D057167:Claudins / Q000235:genetics*; D019295:Computational Biology; D017931:DNA Primers; D060467:Disease Resistance / Q000235:genetics; D055030:Drug Users; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000821:virology*; D016174:Hepacivirus; D006526:Hepatitis C / Q000235:genetics* / Q000635:transmission*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062793:Occludin / Q000235:genetics*; D051122:Scavenger Receptors, Class B / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015819:Substance Abuse, Intravenous
chemical_list: C524757:CLDN9 protein, human; D057167:Claudins; D017931:DNA Primers; C568985:OCLN protein, human; D062793:Occludin; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C122101:claudin 6