title: Claudin-1 gene variants and susceptibility to hepatitis C infection in HIV-1 infected intravenous drug users (an ANRS case-control study).
abstract: Hepatitis C virus (HCV) seroprevalence is highly diverse among human immunodeficiency virus-1 (HIV-1) infected patients, ranging between 10% of HIV-1 infected homo-bisexuel men, to >92% in patients infected with HIV-1 who acquired HIV-1 through intravenous drug use. Thus, being HCV-free while having acquired HIV-1 via intravenous drug use is a rare situation. Claudin-1 is a protein involved in intracellular tight-junctions and has been identified as a major cellular co-receptor for HCV infection. Our objective was to determine whether Claudin-1 gene (CLDN1) mutations might be involved in natural resistance to HCV infection. We conducted a case-control study. All recruited patients acquired HIV-1 infection via intravenous drug use route before 1995. The case study patients remained free from HCV infection (negative anti-HCV antibodies and HCV-RNA). The control study patients was co-infected with HCV (positive anti-HCV antibodies). Direct genomic sequencing of the CLDN1 gene coding region and adjacent intron/exons junctions was performed from peripheral blood mononuclear cells. A total of 138 Caucasian patients were enrolled. Twenty-two patients (cases) were free from HCV infection and 116 (controls) were co-infected with HCV. We found single nucleotide polymorphisms (SNPs) described previously with no significant differences in allele frequencies between cases and controls. In conclusion, despite being a major cellular co-receptor for HCV entry in vitro, we did not identify any specific substitution in CLDN1 gene coding region in our study patients highly exposed but resistant to HCV infection in vivo. Other cellular co-factors involved in HCV infection should be investigated in this highly-exposed intravenous drug users patients.
authors.affiliation: APHP, Department of Internal Medicine and Infectious Diseases, Bicetre University Hospital, Le Kremlin-Bicêtre, France; Paris Descartes, Universiy, Necker Medical School, Sorbonne Paris Cité, Paris, France.
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Baptiste
authors.initials: B
authors.lastname: Fouquet
authors.forename: Yann
authors.initials: Y
authors.lastname: Quertainmont
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon
authors.forename: Sabrinel
authors.initials: S
authors.lastname: Sahali
authors.forename: Christophe
authors.initials: C
authors.lastname: Rioux
authors.forename: Claudine
authors.initials: C
authors.lastname: Duvivier
authors.forename: Martine
authors.initials: M
authors.lastname: Mole
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Micheline
authors.initials: M
authors.lastname: Misrahi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D062445:Claudin-1 / Q000235:genetics*; D060467:Disease Resistance; D055030:Drug Users; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006526:Hepatitis C / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D015819:Substance Abuse, Intravenous / Q000150:complications*; D055815:Young Adult
chemical_list: D062445:Claudin-1
keywords: Claudin-1; HCV entry; HIV; intravenous drug users; natural resistance