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Steven Zeichner, MD, PhD Professor of Microbiology and Tropical Medicine and Pediatrics publications, contact information Research Interests My lab studies viral pathogenesis at a molecular level, with a focus on understanding the interactions of viruses and their host cells. We study human immunodeficiency virus 1 (HIV-1) and Kaposi’s sarcoma-associated herpesvirus (KSHV; Human herpesvirus-8, HHV-8). In our HIV-1 research we are studying how host cell functions contribute to the maintenance of HIV latency. We have shown that cell lines latently infected with HIV exhibit different gene expression patterns than their uninfected parental cells. We hypothesized that these differences resulted from selection for the differential expression of genes that help maintain HIV latency during the production and cloning of the latently infected cell lines. We further hypothesized that treating the latently infected cell lines with small molecule agents that target the products of the differentially expressed genes would eject the virus out of latency, and we showed that the agents could, in fact, activate HIV replication in the latently infected cells. We are now continuing this line of research, identifying additional cellular genes that help control HIV latency and identifying additional small molecule agents targeting the products of those genes that can activate HIV out of latency. We have also studied how certain HIV gene products, such as Vpr, affect host cell physiology and alter host cell signal transduction pathways. In our KSHV work we are conducting detailed studies of the viral gene expression program using a purpose-built KSHV long oligonucleotide microarray system we developed. We have used our KSHV microarrays to produce a detailed kinetic description of the KSHV gene expression program and to dissect the KSHV gene expression program using inhibitors of KSHV replication that act a discrete points in the viral replication cycle. We have also studied the effect of important known KSHV regulatory genes, such as the KSHV Rta (ORF50), on the KSHV gene expression program. We are now continuing this work by studying how additional KSHV regulatory genes and selected host cell treatments affect the KSHV gene expression program, and by conducting experiments to understand how such alterations in the KSHV gene expression program may contribute to the pathogenesis of KSHV-associated diseases. Selected Publications Top Yoshizuka, N, Yoshizuka-Chadani, Y, Krishnan, V, Zeichner, SL. HIV-1 Vpr-dependent cell cycle arrest through a mitogen activated protein kinase signal transduction pathway. J. Virol. 79: 11366-11381 2005 Krishnan, V and Zeichner, SL. Alterations in the expression of DEAD-box and other RNA binding proteins during HIV-1 replication. Retrovirology, 1:42 2004 Lu, M, Suen, J, Frias, C, Pfeiffer, R, Tsai, M-H, Chuang, E, Zeichner, S. Dissection of the Kaposi’s sarcoma-associated herpesvirus gene expression program using the viral DNA replication inhibitor cidofovir. J Virol, 78:13637-13652 2004 Bentley K, Deacon N, Sonza S, Zeichner S, Churchill M. Mutational analysis of the HIV-1 LTR as a promoter of negative sense transcription. Arch Virol, 45:1223-38 2004 Krishnan, V and Zeichner, SL. Host cell gene expression during HIV-1 latency and reactivation, and effects of targeting genes differentially expressed in viral latency. J Virol, 78: 9458-9473 2004 Suscovich, TJ, Paulose-Murphy, M, Harlow, JD, Chen, Y, Thomas, SY, Walker, BD, Scadden , DT, Zeichner, S, Brander, C. Defective immune function of primary effusion lymphoma cells is associated with distinct KSHV gene expression profiles. Leukemia and Lymphoma, 45: 1223 – 1238 2004 Nakamura, H, Lu, M, Gwack, Y, Souvlis, J, Zeichner, SL, and Jung, J. Global Changes in KSHV gene expression patterns following expression of a tetracycline-inducible Rta transactivator. J Virol 77:4205-4220 2003 Lee, B-S, Paulose-Murphy, M, Chung. Y-H, Zeichner, S, Jung, J. Suppression of tetradecanoyl phorbol acetate-induced lytic reactivation of Kaposi’s sarcoma-associated herpesvirus by K1 signal transduction. J Virol 76: 12185-12199 2002 Zhang, P, Ng, P, Caridha, D, Leach, RA, Asher, LV, Novak, MJ, Smith, WJ, Zeichner, SL, Chiang, PK. Gene expression in Jurkat cells poisoned by a sulfur mustard vesicant and the induction of apoptosis. Brit J Pharmacol 237:245-252 2002 Ng, PWP, Iwanaga, Y, Iha, H, Bittner, M, Chen, Y, Jiang, Y, Gooden, G, Trent, JM, Meltzer, P, Jeang, KT, Zeichner, SL. Genome-wide expression changes induced by HTLV-1 Tax. Evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kB activation. Oncogene, 20:4484-4496 2001 Paulose-Murphy, M, Ha, N-K, Xiang, C, Chen, Y, Gillim, L, Yarchoan, R, Meltzer, P, Bittner, M, Trent, J, Zeichner, S. The Transcription program of human herpesvirus-8 (Kaposi’s sarcoma-associated herpesvirus). J Virol 75:4843-4853 2001 Contact Information Top Steven Zeichner, MD, PhD phone: 202-476-6131
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