title: Low cross-neutralization of hepatitis C correlates with liver disease in immunocompromized patients.
abstract: OBJECTIVE
  Chronic hepatitis C virus (HCV) infection causes severe liver disease in HIV-infected patients and liver transplant recipients. The impact of serum and immunoglobulin on viral entry was analysed in these patients.
  
  
  METHODS
  Sera from 60 anti-HCV positive patients, including 30 who were also anti-HIV positive, were tested with HCVpp from different genotypes (1a, 1b, 3 and 4) and with HCVcc (H77/JFH1). Seventeen HIV-seropositive and 13 HIV-seronegative patients with decompensated liver disease were studied before and after liver transplant.
  
  
  RESULTS
  Serum neutralization was markedly lower after liver transplant and in HIV patients than in mono-infected immune-competent individuals. This effect was due to low antibody-mediated neutralization. In HIV patients, low neutralization was correlated with low lymphocyte T CD4 cell counts and the severity of liver disease. To characterize neutralization, we tested HCVpp lacking hypervariable region (HVR1) and SR-BI receptor cholesterol transfer inhibition by BLT-4. These experiments showed that neutralization was strongly dependent on the HVR1 and the SR-BI receptor. HVR1 sequences showed that selective pressures were low in immune-compromised patients and highly correlated to HCV neutralization after liver transplant. Neutralization experiments were reproduced with HCV strain JFH1.
  
  
  CONCLUSIONS
  Serum neutralization in HIV-coinfected patients and HCV-infected liver transplant recipients is poor enhancing HCV entry through HVR1/SR-BI interplay. This may contribute to the severity of hepatitis C in these settings.
authors.affiliation: aUniversité de Lyon, UCB-Lyon1, IFR128, Lyon, F-69007; INSERM, U758, Lyon, F-69007; Ecole Normale Supérieure de Lyon, Lyon, F-69007 bEA 4271 University Nantes cUnité INSERM 955 Créteil dUnité INSERM 785 Villejuif, France. *Dimitri Lavillette and Cyrille Féray contributed equally to the writing of the article.
authors.forename: Guillemette
authors.initials: G
authors.lastname: Maurin
authors.forename: Boris
authors.initials: B
authors.lastname: Halgand
authors.forename: Patrice
authors.initials: P
authors.lastname: Bruscella
authors.forename: Judith
authors.initials: J
authors.lastname: Fresquet
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Duclos-Vallée
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Roque-Afonso
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
authors.forename: Cyrille
authors.initials: C
authors.lastname: Féray
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology* / Q000502:physiology; D018937:Hepatitis C Antibodies / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D016867:Immunocompromised Host; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D012189:Retrospective Studies; D053586:Virus Internalization
chemical_list: D057134:Antibodies, Neutralizing; D018937:Hepatitis C Antibodies