Abstract

CD4 is an integral membrane protein of human helper T lymphocytes that serves as an essential component of the receptor for the human immunodeficiency virus (HIV), the causative agent of human immunodeficiency syndrome (AIDS). HIV binding and fusion with the cell are mediated by specific interaction between the external subunit of the viral envelope glycoprotein (gp120) and CD4 on the target cell surface. We are interested in determining the nature of the binding interaction and using this information to develop therapeutic agents. During the past year we have demonstrated that a truncated 180-amino acid fragment of CD4 contains the epitopes for several monoclonal antibodies that block HIV binding and that this CD4 fragment can form a specific complex with gp120. A recombinant fusion protein containing the CD4 binding site and portions of the Pseudomonas exotoxin A selectivity killed cells infected with HIV and/or expressing the HIV envelope protein. This fusion protein has potential for AIDS chemotherapy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000538-02
Application #
3818304
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Salzwedel, Karl; Berger, Edward A (2009) Complementation of diverse HIV-1 Env defects through cooperative subunit interactions: a general property of the functional trimer. Retrovirology 6:75
Berger, Edward A; Alkhatib, Ghalib (2007) HIV gp120 interactions with coreceptors: insights from studies with CCR5-based peptides. Eur J Med Res 12:403-7
Alkhatib, Ghalib; Berger, Edward A (2007) HIV coreceptors: from discovery and designation to new paradigms and promise. Eur J Med Res 12:375-84
Lusso, Paolo; Earl, Patricia L; Sironi, Francesca et al. (2005) Cryptic nature of a conserved, CD4-inducible V3 loop neutralization epitope in the native envelope glycoprotein oligomer of CCR5-restricted, but not CXCR4-using, primary human immunodeficiency virus type 1 strains. J Virol 79:6957-68
Lagenaur, Laurel A; Berger, Edward A (2005) An anti-HIV microbicide comes alive. Proc Natl Acad Sci U S A 102:12294-5
Agrawal, Lokesh; VanHorn-Ali, Zainab; Berger, Edward A et al. (2004) Specific inhibition of HIV-1 coreceptor activity by synthetic peptides corresponding to the predicted extracellular loops of CCR5. Blood 103:1211-7
Dey, Barna; Del Castillo, Christie S; Berger, Edward A (2003) Neutralization of human immunodeficiency virus type 1 by sCD4-17b, a single-chain chimeric protein, based on sequential interaction of gp120 with CD4 and coreceptor. J Virol 77:2859-65
Farber, Joshua M; Berger, Edward A (2002) HIV's response to a CCR5 inhibitor: I'd rather tighten than switch! Proc Natl Acad Sci U S A 99:1749-51
McHugh, Louise; Hu, Stella; Lee, B K et al. (2002) Increased affinity and stability of an anti-HIV-1 envelope immunotoxin by structure-based mutagenesis. J Biol Chem 277:34383-90
Schito, M L; Kennedy, P E; Kowal, R P et al. (2001) A human immunodeficiency virus-transgenic mouse model for assessing interventions that block microbial-induced proviral expression. J Infect Dis 183:1592-600

Showing the most recent 10 out of 17 publications