• Researcher Profile

    Joseph G. Sodroski, MD

     
    Joseph G. Sodroski, MD
     
    Professor of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School

    Office phone: 617-632-3371
    Fax: 617-632-4338
    Email: joseph_sodroski@dfci.harvard.edu

    Preferred contact method: email
     
     

    Research Department

    Cancer Immunology and AIDS

    Area of Research

    HIV-1 Entry into Target Cells, Post-Entry Restrictions to Retrovirus Infection

    Dana-Farber Cancer Institute
    450 Brookline Avenue
    CLS 1010
    Boston, MA 02215

    Other Practice Locations


    450 Brookline Avenue
    CLS 1010
    Boston, MA 02215

    Biography

    Dr. Sodroski received his MD in 1980 from Jefferson Medical College, followed by a research fellowship in Dr. William Haseltine's laboratory at DFCI. In 1984 he joined the faculty of DFCI and Harvard Medical School. His research focuses on the replication and pathogenesis of HIV, and the innate and adaptive host immune response to retrovirus infections.

    Recent Awards

    • Fellow, American Association for the Advancement of Science, 2008
    • Retrovirology Prize (Ming K. Jeang Foundation), 2006
    • Steven F. Degar Memorial Lecture, Yale University, 2006
    • Harvey Lecture, New York, 2005
    • The William Potter Lecture, Thomas Jefferson University, Philadelphia, 2005

    Research

    HIV-1 Entry into Target Cells, Post-Entry Restrictions to Retrovirus Infection

    Human immunodeficiency virus-1 (HIV-1), the cause of acquired immunodeficiency syndrome (AIDS), enters host cells by a process involving the envelope glycoproteins on the outer part of the virus and host cell receptors. Our laboratory has shown that the HIV-1 envelope glycoproteins must first bind the host receptors, CD4 and CCR5/CXCR4, and then fuse the viral membrane and the host cell membrane. This fusion allows the virus to introduce its genes into the target cell and achieve infection. An understanding of how this process occurs may open new avenues for intervention by drugs or by host immune responses. Therefore, this understanding will expedite the development of HIV-1 vaccines, microbicides, and treatments.

    Once expressed in the infected cell, the HIV-1 envelope glycoproteins contribute to the killing of the cell. We are exploring the mechanisms whereby envelope glycoprotein function leads to cell death. We also are investigating the relation between this cell killing and the loss of T lymphocytes during HIV-1 infection of humans. The destruction of T lymphocytes by HIV-1 is central to inducing an immunocompromised state in infected individuals.

    After entering the host cells, retroviruses encounter blocks in the cells of certain species. These blocks are mediated by a protein called TRIM5alpha, which targets the incoming viral capsid. Understanding the mechanism of TRIM5alpha-mediated restriction may allow this aspect of innate intracellular immunity to be manipulated to our advantage. Furthermore, the uncoating of the retroviral capsid is a poorly understood process. Host cell factors that modulate this process, including TRIM5alpha, are under active investigation.

    Select Publications

    • Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P and Sodroski J. The cytoplasmic body component TRIM5alpha restricts human immunodeficiency virus (HIV-1) infection in Old World monkeys. Nature 2004; 427:848-853.
    • Si Z, Madani M, Cox JM, Chruma JJ, Klein JC, Schon A, Phan N, Wang L, Biorn AC, Cocklin S, Chaiken I, Freire E, Smith AB, III and Sodroski J. Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins. Proc Natl Acad Sci USA 2004;101:5036-5041.
    • Stremlau M, Perron M, Lee M, Yuan L, Song B, Javanbakht H, Diaz-Griffero F, Anderson DJ, Sundquist WI and Sodroski J. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci USA 2006;103:5514-19.
    • Li Y, Li X, Stremlau M, Lee M and Sodroski J. Removal of arginine 332 allows human TRIM5alpha to bind human immunodeficiency virus (HIV-1) capsids and to restrict infection. J Virol 2006;80:6738-44.
    • Perron MJ, Stremlau M, Lee M, Javanbakht H, Song B and Sodroski J. The human TRIM5alpha restriction factor mediates accelerated uncoating of the N-tropic murine leukemia virus capsid. J. Virol 2007;81:2138-48.
    • Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang S-H, Yang X, Zhang M-Y, Zwick MB, Arthos J, Burton DR, Dimitrov DS, Sodroski J, Wyatt R, Nabel GJ and Kwong PD. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 2007;445:732-7.
    • Madani N, Schon A, Princiotto AM, LaLonde JM, Courter JR, Soeta T, Ng D, Wang L, Brower ET, Xiang S-H, Kwon YD, Huang C-C, Wyatt R, Kwong PD, Freire E, Smith III AB and Sodroski JG. Small-molecule CD4 mimics interact with a highly conserved pocket on HIV-1 gp120. Structure 2008;16:1689-701.
    • Haim H, Si Z, Madani N, Wang L, Courter JR, Princiotto A, Kassa A, DeGrace M, McGee-Estrada K, Mefford M, Gabuzda D, Smith III AB and Sodroski J. Soluble CD4 and CD4-mimetic compounds inhibit HIV-1 infection by induction of a short-lived activated state. PLoS Pathogens 2009;5:e1000360.
    • Li Y, Kar A and Sodroski J. Target cell type-dependent modulation of human immunodeficiency virus (HIV-1) capsid disassembly by cyclophilin A. J Virol 2009;83:10951-62.
    • Diaz-Griffero F, Qin X-R, Hayashi F, Kigawa T, Finzi A, Sarnak Z, Lienlaf M, Yokoyama S and Sodroski J. A B-box 2 surface patch important for TRIM5alpha self-association, capsid-binding avidity and retrovirus restriction. J Virol 2009;83:10737-51.

    Investigators

    • Si, Zhi-hai, Ph.D.
    • Madani, Navid, Ph.D.
    • Li, Xiang, Ph.D.
    • Xiang, Shi-Hua, Ph.D.

    Trainees

    • Kar, Alak, Ph.D.
    • Kim, Jonghwa, Ph.D.
    • McGee, Kathleen, Ph.D.
    • Pacheco, Beatriz, Ph.D.
    • Tipper, Christopher, Ph.D.
    • Finzi, Andres, Ph.D.
    • Haim, Hillel, M.D., Ph.D.
    • Mao, Youdong, Ph.D.
    • Bollman, Brooke
    • Guth, Charles (Alex)
    • Li, Yuan
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