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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
Journal article   Peer reviewed

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

Emma L Mohr, Jinhua Xiang, James H McLinden, Thomas M Kaufman, Qing Chang, David C Montefiori, Donna Klinzman and Jack T Stapleton
The Journal of immunology (1950), Vol.185(7), pp.4496-4505
10/01/2010
DOI: 10.4049/jimmunol.1001980
PMCID: PMC3544363
PMID: 20826757

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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.
Virion - immunology Rabbits Immunoprecipitation Enzyme-Linked Immunosorbent Assay Cell Separation GB virus C - immunology Humans Molecular Mimicry - immunology Cross Reactions Antibodies, Neutralizing - immunology HIV-1 - immunology Animals Flow Cytometry Antibodies, Viral - immunology Viral Envelope Proteins - immunology Mice gag Gene Products, Human Immunodeficiency Virus - immunology

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