Research in this project is directed at understanding the mechanisms of HIV-1 infection, particularly in macrophages, and in developing an effective strategy to prevent and/or inhibit infection. Immunodeficiency, the consequence of HIV-1 infection, predisposes the host to opportunistic infections. In turn, opportunistic infections influence target cell susceptibility to HIV-1 infection and replication.Using M. avium as a model co-pathogen, we have defined multiple viral permissive factors. Moreover, immune activation as occurs in tonsils and non-infectious mucosal inflammatory lesions may also be associated with proximal sites of viral replication. These connections between activation/inflammation and enhancement of HIV-1 infection warrant further elucidation of the factors promoting permissiveness to HIV-1. Adherent human peripheral blood monocyte-derived macrophages were exposed to R5 tropic HIV to enable cell surface interactions, and the macrophages monitored for signal transduction, expression of immediate early genes, and downstream genes associated with viral replication by cDNA microarray analyses. As the association between signaling cascades, gene transcription and macrophage-specific viral dynamics is elucidated, new strategies to interfere with HIV replication and re-infection may emerge. In this regard, one of the genes consistently upregulated in HIV-1 infected macrophages was a differentiation marker, CDKN1A, and regulation of this kinase inhibitor has an impact on viral infection and replication in vitro and may be an important target in therapy.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Intramural Research (Z01)
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Dental & Craniofacial Research
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Greenwell-Wild, Teresa; Vazquez, Nancy; Jin, Wenwen et al. (2009) Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon. Blood 114:1864-74
Mavragani, Clio P; Niewold, Timothy B; Moutsopoulos, Niki M et al. (2007) Augmented interferon-alpha pathway activation in patients with Sjogren's syndrome treated with etanercept. Arthritis Rheum 56:3995-4004
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Moutsopoulos, Niki M; Vazquez, Nancy; Greenwell-Wild, Teresa et al. (2006) Regulation of the tonsil cytokine milieu favors HIV susceptibility. J Leukoc Biol 80:1145-55

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