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

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.

Below:  Schematic representation of of CLDN6, CLDN9, OCLN and SCARB1 genes

Full article at:  http://goo.gl/CxlvOG

By:  

Baptiste Fouquet, Micheline Misrahi

Univ Paris Sud, Faculté de Médecine, Hôpitaux Universitaires Paris Sud, Hopital Bicetre, 94275, Le Kremlin-Bicêtre, France

Jade Ghosn

APHP, Unité Fonctionnelle de Thérapeutique en Immuno-Infectiologie, Hôpitaux Universitaire Paris Centre, Hôpital Hôtel Dieu, Paris, France

Jade Ghosn

Université Paris Descartes, EA 7327, Faculté de Médecine site Necker, Sorbonne Paris Cité, Paris, France

Yann Quertainmont, Jean-François Delfraissy

APHP, Service de Médecine Interne, Hôpitaux Universitaires Paris Sud, Hôpital Bicêtre, 94275, Le Kremlin-Bicêtre, France

Dominique Salmon

APHP, Service de Médecine Interne, Hôpitaux Universitaires Paris Centre, Hôpital Cochin, Paris, France

Christophe Rioux

APHP, Service des Maladies Infectieuses et Tropicales, Hôpitaux Universitaires Paris Nord val de Seine, Hospitalier Bichat-Claude Bernard, Paris, France

Claudine Duvivier

Centre Médical de l’Institut Pasteur, 75015, Paris, France

 

More at:  https://twitter.com/hiv_insight

And: http://twitter.com/Prison_Health