Joseph Sodroski, M.D.

Professor of Pathology

Dana-Farber Cancer Institute
JFB - 824
44 Binney St.
Boston, MA 02115
Tel: 617-632-3371
Fax: 617-632-4338
e-mail:Joseph_Sodroski@dfci.harvard.edu
14 postdoctoral fellows, 4 graduate students

The major interests of the laboratory are the early events in human immunodeficiency virus (HIV-1) infection. Understanding and blocking these early events are critical to interrupting HIV-1 transmission and changing the course of the global AIDS pandemic. The laboratory studies HIV-1 entry into cells, a process that is mediated by the viral envelope glycoproteins. These glycoproteins bind receptors on the target cell and fuse viral and cell membranes. The laboratory is devoted to understanding this process at the molecular level, and identifying and characterizing inhibitors. The interaction of neutralizing antibodies with the HIV-1 envelope glycoproteins is being studied.

In virus-producing cells, expression of the HIV-1 envelope glycoproteins results in cytopathic effects. These toxic effects result from the membrane-fusing activity of the HIV-1 envelope glycoproteins, which results in damage to the host cell membranes. The contribution of these processes to the depletion of CD4-positive T lymphocytes in vivo is being studied.

1. The laboratory is also investigating the molecular events involved in the uncoating of the HIV-1 capsid following the entry of the virus into the host cell. In some mammalian species, tripartite motif (TRIM) proteins have evolved to recognize retroviral capsids and block virus infection. The molecular basis for this novel form of innate intracellular immunity is being pursued.

References:

Etemad-Moghadam B, Rhone D, Steenbeke T, Sun Y, Manola J, Gelman R, Fanton JW, Racz P, Tenner-Racz K, Axthelm M, Letvin N and Sodroski J. Membrane-fusing capacity of the human immunodeficiency virus (HIV-1) envelope proteins determines the efficiency of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus. J Virol 2001;75:5646-55.

Si Z, Madani N, Cox JM, Chruma JJ, Klein JC, Schön 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;101:5036-41.

Stremlau M, Owens CM, Perron MJ, Kiessling M, Autissier P and Sodroski J. The cytoplasmic body component TRIM5α restricts human immunodeficiency virus (HIV-1) infection in Old World monkeys. Nature 2004;427:848-53.

Yang X, Kurteva S, Ren X, Lee S and Sodroski J. The stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1. J Virol 2005;79:12132-47.

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 TRIMα restriction factor. Proc Natl Acad Sci USA 2006;103:5514-19.

Schön A, Madani N, Klein JC, Hubicki A, Ng D, Yang X, Smith AB III, Sodroski J and Freire E. Binding thermodynamics of a low-molecular-weight CD4 mimetic to HIV-1 gp120. Biochemistry 2006;45:10973-80.

Diaz-Griffero F, Kar A, Perron M, Xiang S-H, Javanbakht H, Li X and Sodroski J. Modulation of retroviral restriction and proteasome inhibitor-resistant turnover by changes in the TRIM5α B-box 2 domain. J Virol 2007;81:10362-78.