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Characterization of anti-HIV activity mediated by R88-APOBEC3G mutant fusion proteins in CD4+ T cells, peripheral blood mononuclear cells, and macrophages.

ABSTRACT: In this study, we characterized the anti-HIV activities of various R88-APOBEC3G (R88-A3G) mutant fusion proteins in which each A3G mutant was fused with a virus-targeting polypeptide (R14-88, hereafter named R88) derived from HIV-1 Vpr. Our results show that the introduction of the deaminase-defective mutant E259Q into R88-A3G did not affect the virion incorporation of this mutant but blocked the protein's ability to inhibit HIV-1 infection. Our data also reveal that the antiviral effect of A3GY124A, a previously described A3G virus-packaging mutant, was completely rescued when the mutant was fused with R88. In an attempt to identify the most potent R88-A3G fusion proteins against HIV-1 infection, we introduced two Vif-binding mutants (D128K and P129A) into the R88-A3G fusion protein and showed that both R88-A3GD128K and R88-A3GP129A possessed very potent anti-HIV activity. When R88-A3GP129A was transduced into CD4(+) C8166 T cells, HIV-1 infection was completely abolished for at least 24 days. In an attempt to further test the anti-HIV effect of this mutant in primary human HIV susceptible cells, we introduced R88-A3GP129A into human peripheral blood mononuclear cells (PBMCs) and macrophages with a recombinant adeno-associated virus (rAAV2/5) vector. The results demonstrate that a significant inhibition of HIV-1 infection was observed in the transduced PBMCs and macrophages. These results provide evidence for the feasibility of an R88-A3G-based anti-HIV strategy. The further optimization of this system will contribute to the development of new anti-HIV gene therapy approaches.

SUBMITTER: Ao Z

PROVIDER: S-EPMC3205798 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Characterization of anti-HIV activity mediated by R88-APOBEC3G mutant fusion proteins in CD4+ T cells, peripheral blood mononuclear cells, and macrophages.

Ao Zhujun Z Wang Xiaoxia X Bello Alexander A Jayappa Kallesh Danappa KD Yu Zhe Z Fowke Keith K He Xinying X Chen Xi X Li Junhua J Kobinger Gary G Yao Xiaojian X

Human gene therapy 20110318 10

In this study, we characterized the anti-HIV activities of various R88-APOBEC3G (R88-A3G) mutant fusion proteins in which each A3G mutant was fused with a virus-targeting polypeptide (R14-88, hereafter named R88) derived from HIV-1 Vpr. Our results show that the introduction of the deaminase-defective mutant E259Q into R88-A3G did not affect the virion incorporation of this mutant but blocked the protein's ability to inhibit HIV-1 infection. Our data also reveal that the antiviral effect of A3GY ...[more]

PMID: 21182427

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Dataset Information

Characterization of anti-HIV activity mediated by R88-APOBEC3G mutant fusion proteins in CD4+ T cells, peripheral blood mononuclear cells, and macrophages.

Publications

Characterization of anti-HIV activity mediated by R88-APOBEC3G mutant fusion proteins in CD4+ T cells, peripheral blood mononuclear cells, and macrophages.

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