Gregory A. Viglianti, Ph.D.
Associate Professor of Microbiology
72 East Concord Street
Office: R510; 617-638-7790
Lab: R505; 617-638-7792
B.A. Lafayette College
Ph.D. University of Minnesota
Research in the Viglianti laboratory focuses on two main areas: 1) co-factors that influence the mucosal transmission of HIV-1; and 2) the role of endogenous nucleic acid autoantigens as mediators of systemic lupus erythematosus.
1) Mucosal immune responses of the lower female reproductive tract to sexually transmitted pathogenic microorganisms leads to an inflammatory response that enhances the heterosexual transmission of HIV-1. Inflammation is initiated largely by signaling through members of the Toll-like family of innate immune receptors that are activated by pathogen-encoded ligands. This inflammatory response enhances HIV-1 transmission by inducing the recruitment of target immune cells such as Langerhans/dendritic cells (LC/DC), macrophages (MØ)‚ and T lymphocytes to the mucosa and by direct activation of these cells. Recent findings have demonstrated that activation of certain nuclear receptors (NR), including peroxisome proliferator activated receptor (PPAR), liver X receptor (LXR), and glucocorticoid receptor (GR)) potently inhibits TLR-induced inflammatory gene expression in MØ, LC/DC, and epithelial cells. Studies in our laboratory are directed toward evaluating the ability of ligand-activated NR to inhibit the mucosal transmission of HIV-1 and to determine the molecular mechanism(s) of how ligand-activated NR inhibit TLR-induced transcription of both HIV-1 and inflammatory cytokine genes.
2) Autoimmune diseases such as systemic lupus erythematosus (SLE) are characterized by the overproduction of antibodies, many of which recognize ribonucleoprotein and/or chromatin related autoantigens. A common feature of these autoantigens is that they include DNA or RNA. Our laboratory, in collaboration with Dr. Ann Marshak-Rothstein, is defining the protein and nucleic acid composition of these immunostimulatory autoantigens and determining whether different forms of apoptosis are capable of selectively releasing these autoantigens from cells, thereby making them accessible to autoreactive B cells.
- Maciaszek, J.A., S. Coniglio, D.A. Talmage and G.A. Viglianti, 1998. Retinoid induced repression of HIV-1 core promoter activity inhibits virus replication. J. Virol. 72:5862-5869.
- Brown, X.Q., Hanley, T. and Viglianti, G.A. 2002. Interleukin 1beta and interleukin 6 potentiate retinoic acid mediated repression of HIV-1 replication in macrophages.AIDS Res Hum Retroviruses. 18:(9) 649-656.
- Gallina, A. Hanley,T.M., Mandel,R., Trahey,M., Broder,C.C., Viglianti,G.A., and Ryser, H.J.P. 2002. Inhibitors of protein disulfide isomerase prevent cleavage of disulfide bonds in receptor-bound glycoprotein 120 and prevent HIV-1 entry. J.Biol.Chem.277:50579-50588.
- Viglianti, G.A. C.M. Lau, T.M. Hanley, B.A. Miko, M.J. Schlomchik and A. Marshak-Rothstein. 2003. Activation of Autoreactive B Cells by dsDNA. Immunity 19:837-847.
- Hanley, T.M., Kiefer, H.L.B., Schnitzler, A., Marcello, J.E., and Viglianti, G.A. 2004. Retinoid-dependent restriction of HIV-1 replication in monocyte/macrophages. J. Virol. 78(6):2819-2830.
- Kiefer, H.L.B., Marcello, J., Hanley, T., Karthik, A.G., and Viglianti, G. A. 2004. Retinoic acid inhibition of chromatin remodeling at the human immunodeficiency virus type 1 promoter: Uncoupling of histone acetylation and chromatin remodeling. J. Biol. Chem. 279:43604-43613.
- Marshak-Rothstein, A., Busconi, L., Rifkin, I.R., and Viglianti, G.A. 2004. The stimulation of Toll-like receptors by nuclear antigens: A link between apoptosis and autoimmunity. Rheum. Dis. Clin. N. Amer. 30:559-574.
- Marshak-Rothstein, A., Busconi, L., Lau, C.M., Tabor, A.S., Leadbetter, E.A., Akira, S., Krieg, A.M., Lipford, G.B., Viglianti, G.A., and Rifkin, I.R. 2004. Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells. J. Endotoxin Res. 10:247-251.
- Rifkin, I.R., Leadbetter, E.A., Busconi, L., Viglianti, G., and Marshak-Rothstein, A. 2005. Toll-like receptors, endogenous ligands, and systemic autoimmune disease. Immunol. Rev. 204:27-42.
- Lau, C.M., Broughton, C., Tabor, A.S., Akira, S., Mamula, M., Christensen, S.R., Shlomchik, M.J., Viglianti, G.A., Rifkin, I.R., and Marshak-Rothstein, A. (2005) RNA-Associated Autoantigens Activate B Cells by Combined BCR/Toll-like Receptor 7 Engagement. J. Exp. Med. 202: 1171-1177.
- Busconi, L., Lau, C.M., Tabor, A.S., Uccellini, M.B., Ruhe, Z., Akira, S., Viglianti, G.A., Rifkin, I.R., and Marshak-Rothstein, A. (2006) DNA and RNA autoantigens as autoadjuvants. J. Endotoxin Res. 12:379-384. PMID: 17254393
- Uccellini, M.B., Busconi, L., Green, N.M., Busto, P., Christensen, S.R., Shlomchik, M.J., Marshak-Rothstein, A., and Viglianti, G.A. (2008) Autoreactive B Cells Discriminate CpG-rich and CpG-poor DNA and This Response is Modulated by IFN-a. J. Immunol. 181:5875-5884. PMID: 18941176)
- Yasuda, K., Richez, C., Uccellini, M.B., Richards, R.J., Akira, S., Monestier, M., Corley, R.B., Viglianti, G.A., Marshak-Rothstein, A., and Rifkin I.R. (2009) Requirement for DNA CpG Content in TLR9-dependent Dendritic Cell Activation Induced by DNA-containing Immune Complexes. J. Immunol. 183:3109-3117. PMID: 19648272
- Hanley, T.M., Puryear, W.B., Gummuluru, S., and Viglianti, G.A. (2010) PPARg and LXR Signaling Inhibit Dendritic Cell-mediated HIV-1 Capture and trans-infection. PLoS Pathog. 6(7):e1000981. PMID: 20617179
- Hanley, T.M. and Viglianti, G.A. (2011) Nuclear Receptor Signaling Inhibits HIV-1 Replication in Macrophages through Multiple Trans-Repression Mechanisms. J. Virol. 85:10834j-10850. PMIC: 21849441
- Uccellini, M.B., Buston, P., Debatis, M., Marshak-Rothstein, A., and Viglianti, G.A. (2012) Selective Binding of anti-DNA Antibodies to Native dsDNA Fragments of Differing Sequence. Immunol. Lett. Jan 21 PMID: 22285306.
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