Virology Faculty Member - Joseph Sodroski

Joseph Sodroski

Dana-Farber Cancer Institute
Dept. of Cancer Immunology & AIDS
3 Blackfan Circle - CLS 1010
Boston, MA 2115
Tel: 617-632-3371
Fax: 617-632-4338
Email: joseph_sodroski@dfci.harvard.edu



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. 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.



Last Update: 10/22/2013



Publications

Haim H, Strack B, Kassa A, Madani N, Wang L, Courter JR, Princiotto A, McGee K, Pacheco B, Seaman MS, Smith III AB and Sodroski J. Contribution of intrinsic reactivity of the HIV-1 envelope glycoproteins to CD4-independent infection and global inhibitor sensitivity. PLoS Pathogens 2011;7:e1002101.

Li X, Yeung DF, Fiegen AM and Sodroski J. Determinants of the higher-order association of the restriction factor TRIM5
and other tripartite motif (TRIM) proteins. J Biol Chem 2011;286: 27959-70.

Kwon YD, Finzi A, Wu X, Dogo-isonagie C, Lee L, Moore LR, Schmidt SD, Stuckey J, Yang Y, Zhou T, Zhu J, Vicic DA, Debnath AK, Shapiro L, Bewley CA, Mascola JR, Sodroski J and Kwong PD. Unliganded HIV-1 gp120 core structures assume the CD4-bound conformation with regulation by quaternary interactions and variable loops. Proc Natl Acad Sci USA 2012;109: 5663-5668.

Mao Y, Wang L, Gu C, Herschhorn A, Xiang S-H, Haim H, Yang X and Sodroski J. Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Nature Struct Mol Biol 2012; 19:893-899.

Haim H, Salas I and Sodroski J. Proteolytic processing of the human immunodeficiency virus envelope glycoprotein precursor decreases conformational flexibility. J Virol 2013; 87:1884-9.

Mao Y, Wang L, Gu C, Herschhorn A, Désormeaux A, Finzi A, Xiang S-H and Sodroski J. Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. Proc Natl Acad Sci USA, in the press.



© 2013 by the President and Fellows of Harvard College