Department of Molecular Biology & Genetics

Robert Siliciano - Professor Medicine Broadway Research Building, Office Suite 871 733 N. Broadway Baltimore, MD 21205 Office: 410-955-2958 Fax: 443-287-6218 rsilicia@mail.jhmi.edu

Assistant:

Host-virus interaction in HIV infection
For the staggering number of people infected with HIV-1 (40 million), the best current hope for avoiding the fatal consequences of the infection lies in treatment with highly active antiretroviral therapy (HAART), which consists of combinations of 3-5 drugs that inhibit HIV-1 reverse transcriptase or protease. The benefits of HAART in reducing the morbidity and mortality are clearly documented, but major questions remain about how best to use this therapy and how to make it available to all who need it. Our lab has shown that in the vast majority of patients, current HAART regimens cannot cure the infection as a result of the existence of a very stable reservoir of latent virus in resting memory CD4+ T cells. Because HAART is not curative, the treatment of HIV-1 infection is a lifelong challenge. Unfortunately, problems of drug toxicity and the rapid development of drug resistance make this a formidable problem. We feel that it is imperative that we learn everything we can about how to best utilize this life-prolonging form of treatment. Thus, we feel that analysis of basic mechanisms of viral persistence has had and will continue to have a significant impact on the treatment of HIV-1 infection. In the next several years we will endeavor to understand everything we can about the latent reservoir for HIV-1 and other mechanisms of viral persistence and to translate our work on mechanisms of viral persistence into new appro.

Relevant Publications:	Persaud, D., G. K. Siberry, A. Ahonkhai, J. Kajdas, D. Monie, N. Hutton, D. C. Watson, T. C. Quinn, S. C. Ray, and R. F. Siliciano. Continued production of drug-sensitive HIV-1 in children with undetectable viral loads on combination antiretroviral therapy. J. Virol. 78:968-979 (2004). PubMed Reference Zhang, H., Y. Zhou, C. Alcock, T. Kiefer, D. Monie, J. Siliciano, Q. Li, P. Pham, J. Cofrancesco, D. Persaud, and R. F. Siliciano. A novel single-cell level phenotypic assay for residual drug susceptibility and reduced replication capacity of drug-resistant HIV-1. J. Virol. 78:1718-1729 (2004). PubMed Reference Han,Y. K. Lassen, D. Monie, A. R. Sedaghat, S. Shimoji, X. Liu, T. C. Pierson, J. B. Margolick, R. F. Siliciano,. and J. D. Siliciano. Resting CD4+ T Cells from HIV-1-Infected Individuals Carry Integrated HIV-1 Genomes within Actively Transcribed Host Genes. J. Virol. 78:6122-6133 (2004). PubMed Reference Siliciano, J. D., J. Kajdas, D. Finzi, T. C. Quinn, K. Chadwick, J. B. Margolick, C. Kovacs, S. J. Gange, and R. F. Siliciano. Long term follow-up studies confirm the extraordinary stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nature Med. 9:727-728 (2003). PubMed Reference Shen, A., M. C. Zink, J. L. Mankowski, K. Chadwick, J. B. Margolick, L. M. Carruth , M. Li, J. E. Clements, R. F. Siliciano. Resting CD4+ T lymphocytes but not thymocytes provide a latent reservoir in the SIV/macaque model of HIV-1-infected patients on suppressive highly active antiretroviral therapy (HAART). J. Virol. 77:4938-4949 (2003). PubMed Reference

Graduate Program Affiliations	Biochemistry, Cellular & Molecular Biology (BCMB)