Chemistry and Biochemistry

Gregory F. Burton

Gregory Burton

Office: C203 BNSN
Office Phone: 801-422-4917
Lab Room: E221 BNSN
Lab Phone: 801-422-4085
Email: gburton@chem.byu.edu
Office Hours

Education:

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)

Research:

Burton Lab Group

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. Click here to see an illustration.

Publications: