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. The tonsil represents an unique microenvironment possessing a large reservoir of activated and highly susceptible HIV targets. By isolating and culturing tonsil cells with HIV, phenotypic, functional and molecular correlates of enhanced susceptibility, as compared to less sensitive peripheral blood mononuclear cells, can be established and provide insight into interventional targets. In an extension of these studies, 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 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 was a differentiation marker, CDKN1A, and regulation of this kinase inhibitor has an impact on viral infection and replication.
| 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 |
| Peng, Gang; Greenwell-Wild, Teresa; Nares, Salvador et al. (2007) Myeloid differentiation and susceptibility to HIV-1 are linked to APOBEC3 expression. Blood 110:393-400 |
| Moutsopoulos, Niki M; Nares, Salvador; Nikitakis, Nikolaos et al. (2007) Tonsil epithelial factors may influence oropharyngeal human immunodeficiency virus transmission. Am J Pathol 171:571-9 |
| Peng, Gang; Lei, Ke Jian; Jin, Wenwen et al. (2006) Induction of APOBEC3 family proteins, a defensive maneuver underlying interferon-induced anti-HIV-1 activity. J Exp Med 203:41-6 |
| Moutsopoulos, N M; Greenwell-Wild, T; Wahl, S M (2006) Differential mucosal susceptibility in HIV-1 transmission and infection. Adv Dent Res 19:52-6 |
| Vazquez, Nancy; Greenwell-Wild, Teresa; Rekka, Sofia et al. (2006) Mycobacterium avium-induced SOCS contributes to resistance to IFN-gamma-mediated mycobactericidal activity in human macrophages. J Leukoc Biol 80:1136-44 |
| Wahl, Sharon M; Greenwell-Wild, Teresa; Vazquez, Nancy (2006) HIV accomplices and adversaries in macrophage infection. J Leukoc Biol 80:973-83 |
| Riley, E M; Wahl, S; Perkins, D J et al. (2006) Regulating immunity to malaria. Parasite Immunol 28:35-49 |
| 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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