Abstract

Acquired immune deficiency syndrome (AIDS) is characterized by immune suppression secondary to helper T cell depletion and a high incidence of various malignancies, including Kaposi's sarcoma, B cell lymphomas, and non-Hodgkin's lymphomas. We plan to study the molecular mechanisms of T lymphocyte killing in AIDS using a transient assay in which the specific role of the HTLV-III envelope in syncytium formation and cytopathicity can be dissected. We will examine the contribution of envelope- mediated events to the overall cytotoxicity of HTLV-III infection for T lymphocytes. We will attempt to define envelope domains important for host cell binding and for cell membrane fusion. In addition, host cell molecules that interact with the HTLV-III envelope to form syncytia will be studied. These structure- function studies of the HTLV-III envelope should provide insight into mechanisms of host cell entry by RNA tumor viruses. Furthermore, studies of HTLV-III envelope-mediated cytotoxicity will provide models for investigation of mechanisms of pathogenesis by animal and human leukemia viruses known to cause immunosuppressive disorders in addition to malignancies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024755-02
Application #
3137970
Study Section
(SSS)
Project Start
1987-04-01
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115

  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
Bohl, Christopher; Bowder, Dane; Thompson, Jesse et al. (2013) A twin-cysteine motif in the V2 region of gp120 is associated with SIV envelope trimer stabilization. PLoS One 8:e69406
Medjahed, Halima; Pacheco, Beatriz; Désormeaux, Anik et al. (2013) The HIV-1 gp120 major variable regions modulate cold inactivation. J Virol 87:4103-11
Haim, Hillel; Salas, Ignacio; McGee, Kathleen et al. (2013) Modeling virus- and antibody-specific factors to predict human immunodeficiency virus neutralization efficiency. Cell Host Microbe 14:547-58
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

Showing the most recent 10 out of 121 publications