Neutralizing gp120-specific antibodies kill T cell line-adapted HIV-1 in three different ways: Group 1 MAbs inhibit attachment of virions to the target cell (1 of 7 MAbs tested), Group 2 MAbs inhibit fusion of the virion to the target cell (3 of 7 Mabs tested), and Group 3 Mabs are unique in indirectly inhibiting a post-fusion event (3 of 7 Mabs tested). The investigators argue here that Group 1 and 2 MAbs that inhibit attachment or fusion entry are likely to be most affected by variations in the properties of primary or secondary receptors of target cells, whereas Group 3 MAbs that inhibit a post-fusion step are less likely to be so affected, and are therefore the best choice for passive immunotherapy. Specifically this proposal will determine (a) if Group 3 Mabs also inhibit primary strains of HIV-1 by inhibition of a post-fusion step; (b) what function of the post-fusion virion-core particle of lab strains is inhibited and (c) the mechanism by which Group 3 MAbs bound to the gp120 on the exterior of the virion affect the functioning of the core particle on the other side of the viral membrane. The proposal will focus on the CD4-binding site-specific Fab of the human IgGb12, but will also investigate the V3 loop-specific IgG MAb ICR41.1i, as the different locations of of their epitopes suggest that more than one transmembrane transduction signal and more than one post-fusion function of the viral core may be involved.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1-CSR-F (S1))
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University of Warwick
United Kingdom
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CV4 8-UW
Cheung, Linda; McLain, Lesley; Hollier, Mark J et al. (2005) Part of the C-terminal tail of the envelope gp41 transmembrane glycoprotein of human immunodeficiency virus type 1 is exposed on the surface of infected cells and is involved in virus-mediated cell fusion. J Gen Virol 86:131-8
Dimmock, Nigel J; Hardy, Sam A (2004) Valency of antibody binding to virions and its determination by surface plasmon resonance. Rev Med Virol 14:123-35
Cleveland, S Matthew; McLain, Lesley; Cheung, Linda et al. (2003) A region of the C-terminal tail of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 contains a neutralizing epitope: evidence for its exposure on the surface of the virion. J Gen Virol 84:591-602
Reading, Steven A; Heap, Caroline J; Dimmock, Nigel J (2003) A novel monoclonal antibody specific to the C-terminal tail of the gp41 envelope transmembrane protein of human immunodeficiency virus type 1 that preferentially neutralizes virus after it has attached to the target cell and inhibits the production of inf Virology 315:362-72
Khiytani, Dheeraj K; Dimmock, Nigel J (2002) Characterization of a human immunodeficiency virus type 1 pre-integration complex in which the majority of the cDNA is resistant to DNase I digestion. J Gen Virol 83:2523-32
McLain, L; Brown, J L; Cheung, L et al. (2001) Different effects of a single amino acid substitution on three adjacent epitopes in the gp41 C-terminal tail of a neutralizing antibody escape mutant of human immunodeficiency virus type 1. Arch Virol 146:157-66
McInerney, T L; Dimmock, N J (2001) Postattachment neutralization of a primary strain of HIV type 1 in peripheral blood mononuclear cells is mediated by CD4-specific antibodies but not by a glycoprotein 120-specific antibody that gives potent standard neutralization. AIDS Res Hum Retroviruses 17:1645-54
Edwards, M J; Dimmock, N J (2001) A haemagglutinin (HA1)-specific FAb neutralizes influenza A virus by inhibiting fusion activity. J Gen Virol 82:1387-95
Cleveland, S M; Jones, T D; Dimmock, N J (2000) Properties of a neutralizing antibody that recognizes a conformational form of epitope ERDRD in the gp41 C-terminal tail of human immunodeficiency virus type 1. J Gen Virol 81:1251-60
Cleveland, S M; Buratti, E; Jones, T D et al. (2000) Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response. Virology 266:66-78

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