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Publications (3)11.35 Total impact

  • AIDS research and human retroviruses 01/2011; 27(1):1-3. DOI:10.1089/aid.2010.0156
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    ABSTRACT: Elevated expression of inhibitory receptors on virus-specific T cells has been implicated as a mechanism by which viruses evade host immune surveillance. Blockade of these pathways during chronic infection leads to increased T cell function and improved immune control of viral replication. To explore the association between costimulatory receptors and HIV replication, we examined the expression of programmed death 1 (PD-1), CTLA-4, T cell Ig domain and mucin domain 3 (TIM-3), and CD28 on HIV-specific CD4(+) T cells from HIV-infected subjects. Greater than 30% of HIV-specific CD4(+) T cells from untreated subjects coexpressed PD-1, CTLA-4, and TIM-3, whereas <2% of CMV- or varicella-zoster virus-specific CD4(+) T cells expressed all three receptors. Coexpression of all three inhibitory receptors on HIV-specific CD4(+) T cells was more strongly correlated with viral load compared with the expression of each receptor individually. Suppression of HIV replication with antiretroviral therapy was associated with decreased expression of all three inhibitory receptors on HIV-specific CD4(+) T cells. Surprisingly, a high percentage of HIV-specific CD4(+) T cells that expressed inhibitory receptors also coexpressed CD28. In vitro blockade of PD-1 binding concurrent with stimulation through CD28 synergistically increased HIV-specific CD4(+) T cell proliferation to a greater extent than did either alone. These findings indicate that HIV-specific CD4(+) T cell responses during chronic infection are regulated by complex patterns of coexpressed inhibitory receptors and that the synergistic effect of inhibitory receptor blockade and stimulation of costimulatory receptors could be used for therapeutic augmentation of HIV-specific CD4(+) T cell function.
    The Journal of Immunology 09/2010; 185(5):3007-18. DOI:10.4049/jimmunol.1000156
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    ABSTRACT: Efficient replication of varicella-zoster virus (VZV) in cell culture requires expression of protein encoded by VZV open reading frame 63 (ORF63p). Two-dimensional gel analysis demonstrates that ORF63p is extensively modified. Mass spectroscopy analysis of ORF63p isolated from transiently transfected HEK 293 and stably transfected MeWo cells identified 10 phosphorylated residues. In VZV-infected MeWo cells, only six phosphorylated residues were detected. This report identifies phosphorylation of two previously uncharacterized residues (Ser5 and Ser31) in ORF63p extracted from cells infected with VZV or transfected with an ORF63p expression plasmid. Computational analysis of ORF63p for known kinase substrates did not identify Ser5 or Ser31 as candidate phosphorylation sites, suggesting that either atypical recognition sequences or novel cellular kinases are involved in ORF63p post-translational modification.
    Journal of General Virology 05/2010; 91(Pt 5):1133-7. DOI:10.1099/vir.0.019067-0