个人简介

BS, University of Utah (1975) MS, Brigham Young University (1985) Ph.D., Medical College of Virginia, Virginia Commonwealth University (1989) PostDoctoral, Medical College of Virginia, Virginia Commonwealth University (1989-1991)

研究领域

Biochemistry

Additional research areas: HIV/AIDS, Immunology and Molecular Biology A major concern in the treatment of HIV-infected subjects is the establishment of "reservoirs" or sites where HIV escapes intervention by drugs or the immune system. These sanctuary sites store infectious virus that serves to perpetuate infection. The primary cellular reservoirs in humans consist of latently infected CD4 T lymphocytes, monocytes/macrophages, and follicular dendritic cells (FDCs). Lymphocytes and monocytes/macrophages can be found throughout the body but the FDC is found only in tissue sites such as the lymph nodes and spleen. In these tissues, FDCs are in close proximity to the primary target of HIV, the CD4 T lymphocyte. Moreover, macrophages are also in close proximity to FDCs. Scientists are seeking to understand the contribution of each reservoir to disease maintenance and progression. My research focuses on the largest of the HIV reservoirs, the FDC. Shortly after infection, large quantities of HIV become trapped on the surfaces of FDCs and this virus persists throughout the course of disease until the FDC-network is destroyed. My laboratory focuses on defining the contributions of FDCs to HIV pathogenesis. This work has led to the understanding that virus on FDCs is long-lived and maintained in a highly infectious form. This is remarkable because the FDC itself is not infected and the virus in this reservoir is present on the surface of the cell. In contrast, virus in the other two human reservoirs is internalized and the cells are infected. Because virus on the FDC is not actively infecting this cell, it is not susceptible to treatment with the drugs currently used in therapy. Furthermore, the presence of virus on FDCs confers the ability to escape some immune responses. Thus when infected subjects generate neutralizing antibodies that would otherwise block infection of target cells, virus on the FDCs can cause infection "" even when the dose of neutralizing antibody is in vast excess of that needed to block infection without FDCs. Our work has also led to the understanding that FDCs create a unique microenvironment that enhances infection by increasing the expression of a major HIV co-receptor (CXCR4) on CD4+ lymphocytes, by augmenting HIV transcription in infected cells, and by inhibiting CD4+ T lymphocyte cell death by apoptosis. We discovered that germinal center T cells (CD4+ T cells that reside adjacent to FDCs) can no longer migrate to a specific chemokine, CXCL12, because of FDC-induced inhibition signals. We reason that this inability to respond to this chemokine may increase the likelihood of the T cell being exposed to infectious HIV on FDCs. We are currently working to dissect the signaling molecules resulting in germinal center T cell unresponsiveness to CXCL12. We also study the genetic composition of HIV trapped on FDCs in infected individuals to characterize the contributions of this virus to disease pathogenesis.

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Zhou, X., L. Shapiro, G. Fellingham, B.M. Willardson and G.F. Burton. (2011) "HIV replication in CD4+ T lymphocytes in the presence and absence of Follicular dendritic cells: Inhibition of replication mediated by alpha-1-antrypsin through altered IkappaBalpha ubiquitination." J. Immunol. 186: 3148-3155. Zeng, M., D. Feldman, S. Wietgrefe, P. Southern, T. Schacker, C. Reilly, J. Estes, G.F. Burton, G. Silvestri, J. Liffson, J. Carlis and A. T. Haase. (2011) Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in Immunodeficiency Virus infections. J Clin Invest doi:10.1172/JCI45157. El Shikh, M.E.M, El Sayed, R.M., J.G. Tew and G.F. Burton. (2009) Follicular dendritic cells (B-lymphocyte stimulating) - A20434, In Embryonic Encyclopedia of Life Sciences, John Wiley and Sons, London. PDF Thacker, T.C., X. Zhou, J.D. Estes, Y. Jiang, B.F. Keele, T.S. Elton and G.F. Burton. (2009) Follicular dendritic cells and HIV-1 transcription in CD4+ T cells. J Virol. 83:150-8. PDF Keele, B.F., L. Tazi, S. Gartner, Y. Liu, T.B. Burgon, J.D. Estes,T.C. Thacker, K.A. Crandall. J.C. McArthur and G.F. Burton. (2008) Characterization of the follicular dendritic cell reservoir of Human Immunodeficiency Virus type 1. J. Virol. 82:5548-5561. PDF Burton, G.F. Follicular dendritic cells (FDCs) in HIV/AIDS: virus trapping, retention and the germinal center microenvironment. In: Latent infection by HIV and other Lentiviruses: New approaches and treatment challenges. Ed. Amanda Brown. 2007 Estes, J.D., T.C. Thacker, D.L. Hampton, S.A. Kell, B.F. Keele, E. A. Palenske, K.M. Druey and G.F. Burton. (2004) Follicular dendritic cell regulation of CXCR4-mediated germinal center CD4 T cell migration. J. Immunol. 173:6169-6178. PDF Estes, J.D., B.F. Keele, K. Tenner-Racz, P. Racz, Y. Jiang, T.C. Thacker, S. Gartner and G.F. Burton. (2002) Follicular dendritic cells (FDC) and CXCR4 expression on CD4+ T lymphocytes. J. Immunol. 169: 2313-2322. PDF Burton, G.F., B.F. Keele, J.D. Estes, T.C. Thacker and S. Gartner. (2002) Follicular dendritic cells (FDCs) contributions to HIV pathogenesis. Semin. Immunol. 14:275-284. PDF Smith-Franklin, B.A., B.F. Keele, J.G. Tew, S. Gartner, A.K. Szakal, J.D. Estes, T.C. Thacker and G.F. Burton. (2002) Follicular dendritic cells (FDCs) and the persistence of HIV infectivity: the role of Ab and Fcg Receptors. J. Immunol. 168:2408-2414. PDF Smith, B.A., S. Gartner, Y. Liu, A.S. Perelson, N.I. Stilianakis, B.F. Keele, T.M. Kerkering, A Ferreira-Gonzalez, A.K. Szakal, J.G. Tew, and G.F. Burton, (2001) Persistence of Infectious Human Immunodeficiency Virus on follicular dendritic cells. J. Immunol. 166:690-696. PDF Burton, G.F., A. Masuda, S.L. Heath, B.A. Smith, J.G. Tew and A.K.Szakal. (1997) Follicular dendritic cells (FDC) in retroviral infection: host and pathogen perspectives. Immunol. Rev. 156:185-197. PDF Heath, S., J. Grant Tew, J.G. Tew, A.K. Szakal and G.F. Burton. (1995) Follicular dendritic cells and HIV infectivity. Nature 377:740-744. PDF