Primary Appointment:
 Medicine (Infectious Diseases)

GEBS Cluster Affiliations:
 Immunology, Microbiology, and Virology - IMV

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 689
Rochester, New York 14642

Phone: (585) 275-6515
Fax: (585) 442-9328
E-Mail: Xia_Jin@urmc.rochester.edu

Immune responses to HIV-1; HIV Vaccine Development

Cytotoxic T lymphocytes (CTL) are one of the most important effector cell types in controlling animal and human viral infections in vitro and in vivo. My research interest has primarily focused on the role of CD8+ T cells in the pathogenesis of human immunodeficiency virus (HIV) infection. The experimental approaches we use are to quantify viral-specific CTL in various disease settings using limiting dilution analysis (LDA), tetramer assay, ELISPOT and intracellular cytokine staining (ICS) assay. Currently, while maintaining an interest in the role of CD8+ T cells in the pathogenesis of HIV infection, my laboratory research has shifted to the area of development and validation of therapeutic and preventative vaccines for HIV infection. In addition, we are interested in investigating the impact of highly active antiretroviral therapy (HAART) on HIV-specific cellular immune responses.

The mechanisms by which CD8+ T cells inhibit viral replication are central to the understanding of the immunopathogenesis of HIV infection. There are two major mechanisms by which CD8+ T cells suppress viral replication in vitro. One is direct lysis of infected cells. CTL are thought to kill infected target cells as soon as the viral antigens are expressed and presented on their surface in the context of major histocompatibility complex (MHC) class I molecules. Another is to produce antiviral cytokines, including the elusive CD8+ T-cell antiviral factor (CAF), in a cell-contact-independent manner. How CAF inhibits HIV replication is largely unknown, the identity of this CAF is also unknown. We are exploring the feasibilities of identifying CAF using a combination of genetic and proteomics methodologies.

Wang X, Messerle M, Sapinoro R, Santos K, Hocknell PK, Jin X, Dewhurst S. Murine cytomegalovirus abortively infects human dendritic cells, leading to expression and presentation of virally vectored genes J. Virol. 77:7182-7192, 2003.

Jin X, Gao X, Ramanathan M Jr, Deschenes GR, Nelson GW, O'Brien SJ, Goedert JJ, Ho DD, O'Brien TR, Carrington M. Human immunodeficiency virus type 1 (HIV-1)-specific CD8+-T-cell responses for groups of HIV-1-infected individuals with different HLA-B*35 genotypes. J Virol. 76:12603-10, 2002.

Jin X, Ramanathan M, Barsoum S, Deschenes GR, Ba L, Binley J, Schiller D, Bauer DE, Chen DC, Hurley A, Gebuhrer L, El Habib R, Caudrelier P, Klein M, Zhang L, Ho DD, Markowitz M. Safety and immunogenicity of ALVAC vCP1452 and recombinant gp160 in newly Human Immunodeficiency Virus Type 1-infected patients treated with prolonged highly active antiretroviral therapy. J. Virol. 76: 2206-2216, 2002.

Cherpelis S, Shrivastava I, Gettie A, Jin X, Ho DD, Barnett SW, Stamatatos L. DNA vaccination with the human immunodeficiency virus type 1 SF162DeltaV2 envelope elicits immune responses that offer partial protection from simian/human immunodeficiency virus infection to CD8(+) T-cell-depleted rhesus macaques. J Virol. 75:1547-50, 2001.

Jin X, Ogg G, Bonhoeffer S, Safrit J, Vesanen M, Bauer D, Chen D, Cao Y, Demoitie MA, Zhang L, Markowitz M, Nixon D, McMichael A, Ho DD. An antigenic threshold for maintaining human immunodeficiency virus type 1-specific cytotoxic T lymphocytes. Mol Med. 6:803-9, 2000.

Zhang L, Chung C, Hu BS, He T, Guo Y, Kim AJ, Skulsky E, Jin X, Hurley A, Ramratnam B, Markowitz M, Ho DD. Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy. J Clin Invest. 106:839-45, 2000.

Metzner KJ, Jin X, Lee FV, Gettie A, Bauer DE, Di Mascio M, Perelson AS, Marx PA, Ho DD, Kostrikis LG, Connor RI. Effects of in vivo CD8(+) T cell depletion on virus replication in rhesus macaques immunized with a live, attenuated simian immunodeficiency virus vaccine. J Exp Med. 191:1921-31, 2000.

Jin X, Demoitie MA, Donahoe SM, Ogg GS, Bonhoeffer S, Kakimoto WM, Gillespie G, Moss PA, Dyer W, Kurilla MG, Riddell SR, Downie J, Sullivan JS, McMichael AJ, Workman C, Nixon DF. High frequency of cytomegalovirus-specific cytotoxic T-effector cells in HLA-A*0201-positive subjects during multiple viral coinfections. J Infect Dis. 181:165-75, 2000.

Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, Blanchard J, Irwin CE, Safrit JT, Mittler J, Weinberger L, Kostrikis LG, Zhang L, Perelson AS, Ho DD. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med. 189:991-8, 1999.

Ogg GS, Jin X, Bonhoeffer S, Dunbar PR, Nowak MA, Monard S, Segal JP, Cao Y, Rowland-Jones SL, Cerundolo V, Hurley A, Markowitz M, Ho DD, Nixon DF, McMichael AJ. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279:2103-6, 1998.