Abstract

The synthetic peptides, DP107 and DP178, derived from gp41 ectodomain, have been shown to inhibit HIV-transition to a coiled-coil structure; suggesting that the corresponding region of gp41 undergoes structural rearrangement as an obligate step in membrane fusion. The second peptide, DP178 blocks HIV-1 mediated cell fusion at much lower concentration. The application focuses on the mechanism of action of DP178 by deriving virus """"""""escape"""""""" mutants, and mapping the DP178 interactive sites. Correlations between the binding characteristics and the phenotypic changes of the escape mutants would support the critical role of these interactions in virus life cycle.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI030411-07
Application #
2376340
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Project Start
1990-09-30
Project End
2000-02-29
Budget Start
1997-03-01
Budget End
1998-02-28
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Chen, C H; Greenberg, M L; Bolognesi, D P et al. (2000) Monoclonal antibodies that bind to the core of fusion-active glycoprotein 41. AIDS Res Hum Retroviruses 16:2037-41
Rovinski, B; Dekaban, G A; Cao, S X et al. (1999) Engineering of noninfectious HIV-1-like particles containing mutant gp41 glycoproteins as vaccine candidates that allow vaccinees to be distinguished from HIV-1 infectees. Virology 257:438-48
Rimsky, L T; Shugars, D C; Matthews, T J (1998) Determinants of human immunodeficiency virus type 1 resistance to gp41-derived inhibitory peptides. J Virol 72:986-93
Shugars, D C; Wild, C T; Greenwell, T K et al. (1996) Biophysical characterization of recombinant proteins expressing the leucine zipper-like domain of the human immunodeficiency virus type 1 transmembrane protein gp41. J Virol 70:2982-91
Wild, C; Greenwell, T; Shugars, D et al. (1995) The inhibitory activity of an HIV type 1 peptide correlates with its ability to interact with a leucine zipper structure. AIDS Res Hum Retroviruses 11:323-5
Rovinski, B; Rodrigues, L; Cao, S X et al. (1995) Induction of HIV type 1 neutralizing and env-CD4 blocking antibodies by immunization with genetically engineered HIV type 1-like particles containing unprocessed gp160 glycoproteins. AIDS Res Hum Retroviruses 11:1187-95
Chen, C H; Matthews, T J; McDanal, C B et al. (1995) A molecular clasp in the human immunodeficiency virus (HIV) type 1 TM protein determines the anti-HIV activity of gp41 derivatives: implication for viral fusion. J Virol 69:3771-7
Wild, C; Dubay, J W; Greenwell, T et al. (1994) Propensity for a leucine zipper-like domain of human immunodeficiency virus type 1 gp41 to form oligomers correlates with a role in virus-induced fusion rather than assembly of the glycoprotein complex. Proc Natl Acad Sci U S A 91:12676-80
Wild, C T; Shugars, D C; Greenwell, T K et al. (1994) Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc Natl Acad Sci U S A 91:9770-4
Matthews, T J; Wild, C; Chen, C H et al. (1994) Structural rearrangements in the transmembrane glycoprotein after receptor binding. Immunol Rev 140:93-104

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