T cell immunity to human immunodeficiency virus and human herpesvirus type 8

Description of projects available to graduate students:
My laboratory focuses on delineating T cell immunity to two important human pathogens, i.e., human immunodeficiency virus type 1 (HIV-1) and human herpesvirus type 8 (HHV-8/KSHV). AIDS is due to a loss in T cell immunity caused by HIV-1 infection. Although there are new drugs that suppress the virus in many people, these treatments are not a cure. And moreover, there is still no vaccine to prevent HIV-1 infection.

Thus we need to understand how this retrovirus destroys the immune system, particularly the T cell immune response, thus leading to opportunistic infections and cancers defined as AIDS. In addition, one of the major types of AIDS is Kaposi's sarcoma (KS), a blood vessel cell cancer that is caused by HHV-8, a herpesvirus. This cancer may be due in part to loss of T cell immunity to HHV-8, thus allowing the virus to initiate the growth of the cancer cells.

Projects in my lab that are open to new students are:

1. Engineering of dendritic cells (DCs) to enhance T cell immunity to HIV-1.

The goal of this project is to biologically engineer DCs, the most potent antigen-presenting cells, by loading them with different forms of HIV-1 antigens and cytokines and chemokines (proteins that regulate how DCs and T cells function). We are then assessing how these DCs turn on T cells against HIV-1, with ongoing clinical trials using these approaches as therapies to augment the immunity in patients with HIV-1 infection.

A new, exciting aspect of this work is the role of B lymphocytes in transmission of HIV-1 to T cells. We have found that B cells express DC-SIGN, a C type lectin receptor, which binds HIV-1 and enhances down-stream replication of HIV-1 in T cells. We are now defining the molecular pathways involved in this process, which we believe could play a previously unknown, central role in HIV-1 pathogenesis.

2. Delineation of T cell responses to HHV-8/KSHV

Although it is now accepted that HHV-8 causes KS and some other, rare cancers, there is no information on how it does this. We believe that loss of T cell immunity to HHV-8, especially due to HIV-1 infection, is key to development of KS. My lab has developed new assays for measuring T cell immunity to HHV-8 and its potential role in onset of KS and other cancers possibly caused by this virus. A new, very exciting aspect of this work is that we have recently discovered that DC-SIGN serves as a receptor for HHV-8 infection of all types of cells that are targeted by the virus in vivo. This could have importance to the pathogenesis and oncogenicity of the virus.

Techniques graduate student will learn:
T cell and DC functional assays, flow cytometry, cytokine assays, quantitative real-time RT-PCR, immunohistochemistry, confocal microscopy, HIV and HHV-8/KSHV virology, molecular biological assays, electron microscopy.