title: An antibody specific for the C-terminal tail of the gp41 transmembrane protein of human immunodeficiency virus type 1 mediates post-attachment neutralization, probably through inhibition of virus-cell fusion.
abstract: Evidence has been presented which shows that part of the C-terminal tail of the gp41 transmembrane protein of human immunodeficiency virus type 1 (HIV-1) contains a neutralization epitope and is thus exposed on the external surface of the virion. Here, SAR1, a monoclonal antibody, which was stimulated by immunization with a plant virus expressing 60 copies of the GERDRDR sequence from the exposed gp41 tail, and has an unusual pattern of neutralization activity, giving little or no neutralization of free virions, but effecting modest post-attachment neutralization (PAN) of virus bound to target cells was investigated. Here, the properties of PAN were investigated. It was found that PAN could be mediated at 4 or 20 degrees C, but that at 20 degrees C maximum PAN required virus-cell complexes to be incubated for 3 h before addition of antibody. Further PAN appeared stable at 20 degrees C and could be mediated for at least 5 h at this temperature. In contrast, when virus-cell complexes formed at 20 degrees C but then shifted to 37 degrees C for various times before addition of SAR1, PAN was maximal after just 10 min, and was lost after 30 min incubation. Thus, PAN at 37 degrees C is transient and temperature-dependent. Since this scenario recalled the temperature requirements of virus-cell fusion, fusion of HIV-1-infected and non-infected cells was investigated, and it was found that SAR1 inhibited this process by up to 75 %, in a dose-dependent manner. However, antibodies to adjacent epitopes did not inhibit fusion. These data confirm the external location of the SAR1 epitope, implicate the gp41 C-terminal tail in the HIV-1 fusion process for the first time, and suggest that SAR1 mediates PAN by inhibiting virus-mediated fusion.
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Heap
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Reading
authors.affiliation: Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Dimmock
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008561:Membrane Fusion; D009500:Neutralization Tests; D013696:Temperature
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41