Abstract

The HIV-1 envelope glycoproteins play a central role in virus entry into the host cell, in the induction of cytopathic effects, and in the elicitation of an immune response. The goal of this proposal is to understand the relationship between structural features of the HIV-1 envelop glycoproteins and the functions of these molecules during virus infection. The approach that will be taken is to create mutations in HIV-1 envelope glycoprotein regions previously implicated in function. Envelope glycoprotein mutants will be analyzed structurally and functionally with respect to syncytium formation, virus replication and induction of cytopathic effects. Structural studies will be complemented by studying accessibility of selected wild type and mutant envelope glycoprotein regions to monospecific or monoclonal antibodies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI024755-04A1
Application #
3137968
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1987-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02215

  Publications

Richard, Jonathan; Veillette, Maxime; Brassard, Nathalie et al. (2015) CD4 mimetics sensitize HIV-1-infected cells to ADCC. Proc Natl Acad Sci U S A 112:E2687-94
Go, Eden P; Herschhorn, Alon; Gu, Christopher et al. (2015) Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140. J Virol 89:8245-57
Alsahafi, Nirmin; Debbeche, Olfa; Sodroski, Joseph et al. (2015) Effects of the I559P gp41 change on the conformation and function of the human immunodeficiency virus (HIV-1) membrane envelope glycoprotein trimer. PLoS One 10:e0122111
Madani, Navid; Princiotto, Amy M; Schön, Arne et al. (2014) CD4-mimetic small molecules sensitize human immunodeficiency virus to vaccine-elicited antibodies. J Virol 88:6542-55
McGee, Kathleen; Haim, Hillel; Korioth-Schmitz, Birgit et al. (2014) The selection of low envelope glycoprotein reactivity to soluble CD4 and cold during simian-human immunodeficiency virus infection of rhesus macaques. J Virol 88:21-40
Herschhorn, Alon; Gu, Christopher; Espy, Nicole et al. (2014) A broad HIV-1 inhibitor blocks envelope glycoprotein transitions critical for entry. Nat Chem Biol 10:845-52
Mao, Youdong; Wang, Liping; Gu, Christopher et al. (2013) Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. Proc Natl Acad Sci U S A 110:12438-43
Haim, Hillel; Salas, Ignacio; Sodroski, Joseph (2013) Proteolytic processing of the human immunodeficiency virus envelope glycoprotein precursor decreases conformational flexibility. J Virol 87:1884-9
Xiang, Shi-hua; Pacheco, Beatriz; Bowder, Dane et al. (2013) Characterization of a dual-tropic human immunodeficiency virus (HIV-1) strain derived from the prototypical X4 isolate HXBc2. Virology 438:5-13
Désormeaux, Anik; Coutu, Mathieu; Medjahed, Halima et al. (2013) The highly conserved layer-3 component of the HIV-1 gp120 inner domain is critical for CD4-required conformational transitions. J Virol 87:2549-62

Showing the most recent 10 out of 121 publications