Induction of anti-HIV neutralizing antibodies by synthetic peptides.

Chanh, Tran C.; Dreesman, Gordon R.; Kanda, Patrick; Linette, Gerald P.; Sparrow, James T.; Ho, David D.; Kennedy, R C

doi:10.1002/j.1460-2075.1986.tb04607.x

Cited by 224 publications

(114 citation statements)

References 48 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…It is interesting that some antibodies raised against the cytoplasmic tail of human immunodeficiency virus gp41 neutralize infection (2,15). This observation led to the suggestion that these sequences were expressed on cell surfaces, although this proposal is controversial (30).…”

Section: Discussionmentioning

confidence: 99%

Evidence for Mixed Membrane Topology of the Newcastle Disease Virus Fusion Protein

McGinnes

Reitter

Gravel

et al. 2003

J Virol

View full text Add to dashboard Cite

The synthesis of the Newcastle disease virus (NDV) fusion (F) protein in a cell-free protein-synthesizing system containing membranes was characterized. The membrane-associated products were in at least two different topological forms with respect to the membranes. The properties of one form were consistent with the expected membrane insertion as a classical type 1 glycoprotein. This form of the protein was fully glycosylated, and sequences amino terminal to the transmembrane domain were protected from protease digestion by the membranes. The second form of membrane-associated F protein was partially glycosylated and partially protected from protease digestion by the membranes. Protease digestion resulted in a 23-kDa proteaseprotected polypeptide derived from F 2 sequences and sequences from the amino-terminal end of the F 1 domain. Furthermore, a 10-kDa polypeptide derived from the cytoplasmic domain (CT) was also protected from protease digestion by the membranes. Protease resistance of the 23-and 10-kDa polypeptides suggested that this second form of F protein inserted in membranes in a polytopic conformation with both the amino-terminal end and the carboxyl-terminal end translocated across membranes. To determine if this second form of the fusion protein could be found in cells expressing the F protein, two different approaches were taken. A polypeptide with the size of the partially translocated F protein was detected by Western analysis of proteins in total-cell extracts of NDV strain B1 (avirulent)-infected Cos-7 cells. Using antibodies raised against a peptide with sequences from the cytoplasmic domain, CT sequences were detected on surfaces of F proteinexpressing Cos-7 cells by immunofluorescence and by flow cytometry. This antibody also inhibited the fusion of red blood cells to cells expressing F and HN proteins. These results suggest that NDV F protein made both in a cell-free system and in Cos-7 cells may exist in two topological forms with respect to membranes and that the second form of the protein may be involved in cell-cell fusion.

show abstract

Section: Discussionmentioning

confidence: 99%

Evidence for Mixed Membrane Topology of the Newcastle Disease Virus Fusion Protein

McGinnes

Reitter

Gravel

et al. 2003

J Virol

View full text Add to dashboard Cite

show abstract

“…Nevertheless, the external portion of gp4l and perhaps part of p17 have also been reported to be sensitive to neutralizing antibodies (146,222,839,1040) (see Sections XIV F and XXII A). The antibodies to p17 could indicate some protrusion of this core protein to the outside of the virion.…”

Section: Hiv Virionmentioning

confidence: 99%

Pathogenesis of Human Immunodeficiency Virus Infection

Levy¹

1989

Annals of the New York Academy of Sciences

222

290

View full text Add to dashboard Cite

“…In contradiction to this classical model, several studies have described antibodies strongly reacting with a region situated C terminally to the membrane-spanning domain, thought to be located within the cell, in serum samples of HIV-infected patients (6,10,23,30,59). Furthermore, some groups have reported that antibodies against this region are able to modestly neutralize some strains of HIV type 1 (HIV-1) and HIV-2 under modified conditions in vitro (3,9,15,19,25,35,36).…”

mentioning

confidence: 98%

Evidence against Extracellular Exposure of a Highly Immunogenic Region in the C-Terminal Domain of the Simian Immunodeficiency Virus gp41 Transmembrane Protein

Postler

Martinez-Navío

Yuste

et al. 2012

J Virol

View full text Add to dashboard Cite

The generally accepted model for human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein topology includes a single membrane-spanning domain. An alternate model has been proposed which features multiple membrane-spanning domains. Consistent with the alternate model, a high percentage of HIV-1-infected individuals produce unusually robust antibody responses to a region of envelope, the so-called "Kennedy epitope," that in the conventional model should be in the cytoplasm. Here we show analogous, robust antibody responses in simian immunodeficiency virus SIVmac239-infected rhesus macaques to a region of SIVmac239 envelope located in the C-terminal domain, which in the conventional model should be inside the cell. Sera from SIV-infected rhesus macaques consistently reacted with overlapping oligopeptides corresponding to a region located within the cytoplasmic domain of gp41 by the generally accepted model, at intensities comparable to those observed for immunodominant areas of the surface component gp120. Rabbit serum raised against this highly immunogenic region (HIR) reacted with SIV envelope in cell surface-staining experiments, as did monoclonal anti-HIR antibodies isolated from an SIVmac239-infected rhesus macaque. However, control experiments demonstrated that this surface staining could be explained in whole or in part by the release of envelope protein from expressing cells into the supernatant and the subsequent attachment to the surfaces of cells in the culture. Serum and monoclonal antibodies directed against the HIR failed to neutralize even the highly neutralization-sensitive strain SIVmac316. Furthermore, a potential N-linked glycosylation site located close to the HIR and postulated to be outside the cell in the alternate model was not glycosylated. An artificially introduced glycosylation site within the HIR was also not utilized for glycosylation. Together, these data support the conventional model of SIV envelope as a type Ia transmembrane protein with a single membrane-spanning domain and without any extracellular loops.

show abstract

Induction of anti-HIV neutralizing antibodies by synthetic peptides.

Cited by 224 publications

References 48 publications

Evidence for Mixed Membrane Topology of the Newcastle Disease Virus Fusion Protein

Evidence for Mixed Membrane Topology of the Newcastle Disease Virus Fusion Protein

Pathogenesis of Human Immunodeficiency Virus Infection

Evidence against Extracellular Exposure of a Highly Immunogenic Region in the C-Terminal Domain of the Simian Immunodeficiency Virus gp41 Transmembrane Protein

Contact Info

Product

Resources

About