title: Additional glycosylation within a specific hypervariable region of subtype 3a of hepatitis C virus protects against virus neutralization.
abstract: BACKGROUND
  The envelope glycoprotein E2 of hepatitis C virus (HCV) contains several hypervariable regions. Interestingly, 2 regions of intragenotypic hypervariability within E2 have been described as being specific to HCV subtype 3a. Based on their amino acid position in E2, they were named HVR495 and HVR575. Here, we further investigated these regions in order to better understand their role in HCV infection.
  
  
  METHODS
  Sequences of HCV envelope glycoproteins from Pakistani patients infected with subtype 3a were cloned and compared with other subtype 3a sequences. The entry functions and the sensitivity to antibody neutralization of selected HCV glycoprotein sequences were tested in the HCV pseudotyped particles (HCVpp) system. In addition, the cell-cultured HCV system (HCVcc) was also used to confirm some of the data obtained with the HCVpp system.
  
  
  RESULTS
  We observed interesting new features within HVR495 and HVR575 for several subtype 3a isolates. Indeed, changes in glycosylation sites were observed with the appearance of a new glycosylation site within HVR495. Importantly, HCVpp and HCVcc that contained this new HVR495 glycosylation site were less sensitive to antibody neutralization.
  
  
  CONCLUSIONS
  We identified a new glycosylation site within the HVR495 region of HCV subtype 3a that has a protective effect against antibody neutralization.
authors.affiliation: Institut Pasteur de Lille, Center for Infection and Immunity of Lille.
authors.forename: Sadia
authors.initials: S
authors.lastname: Anjum
authors.forename: Ahmed
authors.initials: A
authors.lastname: Wahid
authors.forename: Muhammad Sohail
authors.initials: MS
authors.lastname: Afzal
authors.forename: Anna
authors.initials: A
authors.lastname: Albecka
authors.forename: Khaled
authors.initials: K
authors.lastname: Alsaleh
authors.forename: Tahir
authors.initials: T
authors.lastname: Ahmad
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.forename: Czeslaw
authors.initials: C
authors.lastname: Wychowski
authors.forename: Ishtiaq
authors.initials: I
authors.lastname: Qadri
authors.forename: François
authors.initials: F
authors.lastname: Penin
authors.forename: Jean
authors.initials: J
authors.lastname: Dubuisson
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D006031:Glycosylation; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006526:Hepatitis C / Q000276:immunology / Q000821:virology*; D018937:Hepatitis C Antibodies / Q000276:immunology*; D006801:Humans; D009154:Mutation; D010154:Pakistan; D012367:RNA, Viral / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D060225:Tetraspanin 28 / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; C554798:CD81 protein, human; D000939:Epitopes; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus
keywords: hepacivirus; hepatitis C virus; neutralizing antibodies; sequence variability; viral glycoproteins