Glycosylation Governs the Binding of Antipeptide Antibodies to Regions of Hypervariable Amino Acid Sequence within Recombinant gp120 of Human Immunodeficiency Virus Type 1

Davis, David A.; Stephens, D. M.; Willers, Chrissie; Lachmann, P. J.

doi:10.1099/0022-1317-71-12-2889

Cited by 58 publications

(70 citation statements)

References 35 publications

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“…The phenomenon of masking neutralizing antibody binding sites through the addition and use of a new glycosylation site has been described for the haemagglutinin of influenza virus (Skehel et al, 1984), the E2 glycoprotein of Sindbis virus (Davis et al, 1987), the gpl20 of human immunodeficiency virus (Davis et al, 1990) and HN of the Beaudette isolate of NDV (Yusoff et al, 1988). In the latter instance, the selecting MAb only weakly inhibits HA and does not inhibit NA activity on neuraminlactose.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus

Iorio

Glickman²,

Sheehan³

1992

Journal of General Virology

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The majority of neutralizing monoclonal antibodies (MAbs) to the haemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus prevent attachment of the virus to cellular receptors and inhibits virion-induced fusion from without (FFWO) and fusion from within (FFWI) mediated by the virus glycoprotein-laden infected cell surface. For these antibodies, the inhibition of fusion is presumed to be the result of the prevention of HN-mediated bridging of potential fusion partners. MAbs against antigenic sites 3 and 4 neutralize virus infectivity, but by a mechanism other than the prevention of attachment, the exact nature of which remains to be established. Antibodies to both of these sites effectively inhibit virion-induced FFWO, even when the inducing virus is not infectious. This is consistent with the mechanism of neutralization of these MAbs involving the inhibition of an early, post-attachment step in infection. MAbs to site 3 also inhibit FFWI, but those to site 4 do not, even when added at high concentrations. This suggests that the requirement for HN may be different in the two modes of fusion. The epitopes recognized by MAbs to sites 3 and 4 have been delineated by the identification of individual nucleotide substitutions in the HN genes of neutralization escape variants. Some of the deduced amino acid substitutions result in additional N-linked glycosylation sites in HN, which are utilized and presumably account for the escape from neutralization.

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Section: Discussionmentioning

confidence: 99%

Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus

Iorio

Glickman²,

Sheehan³

1992

Journal of General Virology

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“…However, it is possible that the three closely located or other more distant complexor hybrid-type glycans affect V3 immunological properties. There is also other evidence for the direct role of glycans on V3 biological and immunological properties: (i) when considering vertical HIV transmission, 'a conserved N-linked glycosylation site within the V3 region, present in each mother's sequence set, was absent in all of the infant's sequence set' [37]; (ii) antibodies elicited by V3 peptide (301-315) failed to recognize gp120sr2 but not its unglycosylated counterpart [4]; (iii) resistance of HIV-l to neutralization was achieved by adding glycan in the V3 loop adjacent to the NA binding site [35].…”

Section: Discussionmentioning

confidence: 99%

Effect of sialic acid removal on the antibody response to the third variable domain of human immunodeficiency virus type‐1 envelope glycoprotein

et al. 1994

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AhstraetThe gp160 envelope glycoprotein of human immunodeficiency virus type-l (HIV-l) is an essential component of current vaccine trials. The glycans of gp160, part of which are highly sialylated, have been shown to influence gp160 immunogenicity. Here, using a panel of synthetic V3 peptides, we characterized the anti-V3 antibodies generated in rabbits immunized by desialylated recombinant gp160,,. Amino acid residues flanking the GPGR tip of V3 were necessary for the recognition by anti-V3 antibodies raised against either the native or desialylated gp160. Both types of antibodies reacted to V3 peptides of MN and SF2 strains and with a North American/European V3 consensus peptide, while anti-desialylated gpl60,, antibodies reacted in addition to the V3 of CDC4, WMJ2 and NY5 strains. Yet, the V3 peptides did not signiscantly differ in their secondary structure, as determined by circular dichroism. The titer and avidity for V3,, of anti-desialylated gp160,, antibodies were significantly lower than those of anti-native gp160,, which likely accounts for the inability of anti-desialylated gp160, sera to neutralize HIV-1,Kinduced syncytia. These results indicate that V3 immunogenicity may be iduenced by subtle directed changes in the gpl60 glycosylation pattern.

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“…Cationic polymers are thought to interact with and destroy the cell membrane after permeating the cell wall, resulting in the expression of antibacterial activity (6,10,24). Reports have shown that cationic polymers express antibacterial activity at optimal molecular weights (9,10,24). We thus attempted to investigate the effect of the cationic polymer PEI on HIV-1 infection in vitro.…”

Section: Effect Of Pei On Hiv-1 Entrymentioning

confidence: 99%

“…We obtained the same tendency Cationic polymers are known to possess potential antibacterial activity, and it has been suggested that the target site of action is the bacterial cell membrane. Cationic polymers are thought to interact with and destroy the cell membrane after permeating the cell wall, resulting in the expression of antibacterial activity (6,10,24). Reports have shown that cationic polymers express antibacterial activity at optimal molecular weights (9,10,24).…”

Section: Effect Of Pei On Hiv-1 Entrymentioning

confidence: 99%

“…Among the HIV-1 proteins, gp120 and gp41 show the greatest variation. Analyses of gp120 and gp41 from several HIV-1 isolates have shown that gp120 contains five hypervariable regions separated by relatively conserved regions (10,20,34,40). HIV binds to CD4-positive cells such as helper T cells or monocytes/ macrophages (14,42) with the aid of gp120, and thus it is apparent that the CD4 molecule is a primary receptor for HIV.…”

mentioning

confidence: 99%

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Enhancement of Human Immunodeficiency Virus Type 1 (HIV‐1) Infection via Increased Membrane Fluidity by a Cationic Polymer

Owada

Miyashita

Motomura

et al. 1998

Microbiology and Immunology

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Cationic polymers are known to have potent activity against bacteria, but their effects on viral activity have been little studied. We investigated the effect of one such polymer, polyethyleneimine (PEI), on HIV-1 infection. Although virus-cell binding was significantly inhibited by PEI, HIV-1 infection in human T-cell lines such as MT-4 and MOLT-4 was accelerated conversely when the drug treatment was carried out, after the virus had attached to the cells or PEI was simultaneously added to the virus and cell culture system. This paradoxical effect of PEI on HIV-1 infection was examined using HIV-1 chronically infected cells (MOLT-4/HIV-1). Dissociation of the glycoprotein gp120 (as revealed by exposure of transmembrane protein gp41) from MOLT-4/HIV-1 cells and the resultant fusion of these cells was shown to be induced by the addition of PEI. Accordingly, it was suggested that the binding inhibition of HIV-1 to CD4-positive cells by PEI was due to the shedding of gp120 from HIV-1 particles, and this PEI rather promoted membrane fusion between the virus and cells leading to the enhancement of HIV-1 infection. Similarly, dissociation of gp120 from MOLT-4/HIV-1 was also induced by sCD4. The effect of these reagents on changes in membrane fluidity was evaluated by polarization (p) measurements, and it was observed that the acceleration of membrane fluidity occurred only in the PEI system. Therefore, it is likely that PEI accelerates HIV-1 infection by facilitating virus entry into the host cells through an increase in membrane fluidity.

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Glycosylation Governs the Binding of Antipeptide Antibodies to Regions of Hypervariable Amino Acid Sequence within Recombinant gp120 of Human Immunodeficiency Virus Type 1

Cited by 58 publications

References 35 publications

Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus

Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus

Effect of sialic acid removal on the antibody response to the third variable domain of human immunodeficiency virus type‐1 envelope glycoprotein

Enhancement of Human Immunodeficiency Virus Type 1 (HIV‐1) Infection via Increased Membrane Fluidity by a Cationic Polymer

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