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The research in my laboratory focuses on mechanisms of human immunodeficiency virus type 1 (HIV-1) replication and pathogenesis.  HIV-1 replication is continuous and unrelenting throughout the course of infection, despite vigorous anti-viral humoral and cellular immune responses by the host.  Our long-term goals are to understand how HIV-1 exploits, disrupts, and evades the immune response for transmission, replication, and persistence, and to elucidate the effects of genetic variation on viral fitness.

Our work on HIV-1 can be divided into three major areas.  First, because there is no model system to directly explore questions about HIV-1 infection in vivo, we use the SIV-macaque model for studies about pathogenesis.  A unique set of SIV variants cloned from different stages of infection and disease provide the basis for these studies.  Using these viruses, we have shown that variants emerging during the course of infection influence viral load and the rate of disease progression.  Currently, we are dissecting the pathogenic determinants of SIV variants and determining how these mutations influence viral fitness during both transmission and persistent infection.  Related studies are pursued using primary HIV-1 variants from cohorts of HIV-1 infected patients.  Second, we are investigating how HIV-1 and SIV exploit macrophages and dendritic cells to facilitate infection and replication in CD4+ T-cells.  Third, we have begun molecular studies to identify and characterize cellular factors that either positively or negatively regulate HIV-1 and SIV replication.

Recent Publications (PubMed)

• Kimata, JT, L Kuller, D Anderson, P Dailey, and J Overbaugh.  Emerging cytopathic and antigenic SIV variants influence AIDS progression.  Nature Med 5:535-541, (1999).

  Yu Kimata MT, M Cella, JE Biggins, C Rorex, R White, S Hicks, JM Wilson, PG Patel, J Allan, M Colonna, and JT Kimata.  Capture and transfer of simian immunodeficiency virus by macaque dendritic cells is enhanced by DC-SIGN.  J Virol 76:11827-11836 (2002).

  Kimata, JT, JM Wilson, and PG Patel.  The increased replicative fitness of a late-stage simian immunodeficiency virus mne variant is evident in macrophage- or dendritic cell-T-cell cocultures.  Virology 327:307-317 (2004).

  Kimata, JT.  HIV fitness and disease progression:  Insights from the SIV-macaque model.  Current HIV Research 4:65-77 (2006).

  Liu H, EC Dow, R Arora, JT Kimata, LM Bull, RC Arduino, and AP Rice.  Integration of human immunodeficiency virus type 1 in untreated infection occurs preferentially within genes.  J Virol 80:7765-7768 (2006).

  Lee S, R Arora, LM Bull, RC Arduino, L Garza, JS Allan, JT Kimata, and P Zhou.  A non-neutralizing anti-HIV-1 antibody turns into a broad neutralizing antibody when expressed on the surface of HIV-1-susceptible cells (II): inhibition of HIV-1 captured and transferred by DC-SIGN.  AIDS Res Human Retroviruses 22:874-883 (2006).

  Biggins, JE, T Biesinger, MT Yu Kimata, R Arora, and JT Kimata. ICAM-3 influences human immunodeficiency virus type 1 replication in CD4+ T-cells independent of DC-SIGN-mediated transmission.  Virology 364:383-394 (2007).

  Ambrose Z, S Palmer, VF Boltz, M Kearney, K Larson, P Polacino, L Flanary, K Oswald, M Piatak, Jr, J Smedley, W Shao, N Bischofberger, F Maldarelli, JT Kimata, JW Mellors, SL Hu, JM Coffin, JD Lifson, and VN KewalRamani.  Suppression of viremia and evolution of HIV-1 drug resistance in a macaque model for antiretroviral therapy. J Virol 81:12145-12155 (2007).

  Biesinger T, MT Yu Kimata, and JT Kimata. Changes in simian immunodeficiency virus reverse transcriptase alleles that appear during infection of macaques enhance infectivity and replication in CD4+ T-cells.  Virology 370:184-193 (2008).