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.
The approximately 150 amino acid C-terminal tail of the gp41 transmembrane glycoprotein of human immunodeficiency virus type 1 (HIV-1) is generally thought to be located inside the virion. However, we show here that both monoclonal IgG and polyclonal epitope-purified IgG specific for the (746)ERDRD(750) epitope that lies within the C-terminal tail neutralized infectious virus. IgG was mapped to the C-terminal tail by its failure to neutralize tail-deleted virus, and by sequencing of antibody-escape mutants. The fact that antibody does not cross lipid membranes, and infectious virus is by definition intact, suggested that ERDRD was exposed on the surface of the virion. This was confirmed by reacting virus and IgG, separating virus and unbound IgG by centrifugation, and showing that virus was neutralized to essentially the same extent as virus that had been in constant contact with antibody. Epitope exposure on virions was independent of temperature and therefore constitutive. Monoclonal antibodies specific to epitopes PDRPEG and IEEE, upstream of ERDRD, also bound to virions, suggesting that they too were located externally. Protease digestion destroyed the ERDRD and PDRPEG epitopes, consistent with their proposed external location. Altogether these data are consistent with part of the C-terminal tail of gp41 being exposed on the outside of the virion. Possible models of the structure of the gp41 tail, taking these observations into account, are discussed.
Cleveland
S Matthew
SM
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
McLain
Lesley
L
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
Cheung
Linda
L
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
Jones
Tim D
TD
Axis Genetics, Babraham, Cambridge CB2 4AZ, UK.
Hollier
Mark
M
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
Dimmock
Nigel J
NJ
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK.
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D010450:Endopeptidases; D018604:Epitope Mapping; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests
D000914:Antibodies, Viral; D000939:Epitopes; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D010450:Endopeptidases