title: GB virus type C envelope protein E2 elicits antibodies that react with a cellular antigen on HIV-1 particles and neutralize diverse HIV-1 isolates.
abstract: Broadly neutralizing Abs to HIV-1 are well described; however, identification of Ags that elicit these Abs has proven difficult. Persistent infection with GB virus type C (GBV-C) is associated with prolonged survival in HIV-1-infected individuals, and among those without HIV-1 viremia, the presence of Ab to GBV-C glycoprotein E2 is also associated with survival. GBV-C E2 protein inhibits HIV-1 entry, and an antigenic peptide within E2 interferes with gp41-induced membrane perturbations in vitro, suggesting the possibility of structural mimicry between GBV-C E2 protein and HIV-1 particles. Naturally occurring human and experimentally induced GBV-C E2 Abs were examined for their ability to neutralize infectious HIV-1 particles and HIV-1-enveloped pseudovirus particles. All GBV-C E2 Abs neutralized diverse isolates of HIV-1 with the exception of rabbit anti-peptide Abs raised against a synthetic GBV-C E2 peptide. Rabbit anti-GBV-C E2 Abs neutralized HIV-1-pseudotyped retrovirus particles but not HIV-1-pseudotyped vesicular stomatitis virus particles, and E2 Abs immune-precipitated HIV-1 gag particles containing the vesicular stomatitis virus type G envelope, HIV-1 envelope, GBV-C envelope, or no viral envelope. The Abs did not neutralize or immune-precipitate mumps or yellow fever viruses. Rabbit GBV-C E2 Abs inhibited HIV attachment to cells but did not inhibit entry following attachment. Taken together, these data indicate that the GBV-C E2 protein has a structural motif that elicits Abs that cross-react with a cellular Ag present on retrovirus particles, independent of HIV-1 envelope glycoproteins. The data provide evidence that a heterologous viral protein can induce HIV-1-neutralizing Abs.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Mohr
authors.forename: Jinhua
authors.initials: J
authors.lastname: Xiang
authors.forename: James H
authors.initials: JH
authors.lastname: McLinden
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kaufman
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Donna
authors.initials: D
authors.lastname: Klinzman
authors.forename: Jack T
authors.initials: JT
authors.lastname: Stapleton
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002469:Cell Separation; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D029407:GB virus C / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D018716:Molecular Mimicry / Q000276:immunology; D011817:Rabbits; D014759:Viral Envelope Proteins / Q000276:immunology*; D014771:Virion / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
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