Joseph G. Sodroski


Dana Farber Cancer Institute
44 Binney Street
CLS Building, Room 1010
Boston, MA 02115
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.

References:

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 TRIM5α restriction factor. Proc Natl Acad Sci USA 2006;103:5514-19.

Li X and Sodroski J. The TRIM5α B-box 2 domain promotes cooperative binding to the retroviral capsid by mediating higher-order self-association. J Virol 2008;82:11495-502.

Madani N, Schön 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.

Kassa A, Finzi A, Pancera M, Courter JR, Smith AB III, Sodroski J. Identification of a human immunodeficiency virus (HIV-1) envelope glycoprotein variant resistant to cold inactivation. J Virol 2009;83:4476-88.

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.

Xiang S-H, Finzi A, Pacheco B, Alexander K, Yuan W, Rizzuto C, Huang C-C, Kwong PD and Sodroski J. A V3 loop-dependent gp120 element disrupted by CD4 binding stabilizes the human immunodeficiency virus (HIV-1) envelope glycoprotein trimer. J Virol 2010;84:3147-61.

Finzi A, Xiang S-H, Pacheco B, Wang L, Haight J, Kassa A, Danek B, Pancera M, Kwong PD and Sodroski J. Topological layers in the HIV-1 gp120 inner domain regulate gp41 interaction and CD4-triggered conformational transitions. Molecular Cell 2010;37:656-67.



Last Update: 1/6/2014