HIV gp120 V1/V2 and C2-V3 domains glycoprotein compatibility is required for viral replication

Chen, Meisheng; Shi, Chaofu; Kalia, Vandana; Tencza, Sarah Burroughs; Montelaro, Ronald C.; Gupta, Phalguni

doi:10.1016/s0168-1702(01)00322-7

Cited by 12 publications

(11 citation statements)

References 44 publications

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“…The proposed interaction of the EIAV gp90 V3 and V4 domains is further supported by the observation that the gp90V(V3) chimera was replication defective, thus indicating a required compatibility between the V3 and V4 domains of gp90. These observations with EIAV are similar to studies with simian immunodeficiency virus and HIV-1, indicating required compatibility between distinct variable domains, suggesting functional interactions (5).…”

Section: Discussionsupporting

confidence: 80%

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Howe¹,

Leroux

Issel

et al. 2002

J Virol

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Equine infectious anemia virus (EIAV) infection of horses is characterized by well-defined waves of viremiaassociated with the sequential evolution of distinct viral populations displaying extensive envelope gp90 variation; however, a correlation of in vivo envelope evolution with in vitro serum neutralization phenotype remains undefined. Therefore, the goal of the present study was to utilize a previously defined panel of natural variant EIAV envelope isolates from sequential febrile episodes to characterize the effects of envelope variation during persistent infection on viral neutralization phenotypes and to define the determinants of EIAV envelope neutralization specificity. To assess the neutralization phenotypes of the sequential EIAV envelope variants, we determined the sensitivity of five variant envelopes to neutralization by a longitudinal panel of immune serum from the source infected pony. The results indicated that the evolution of the EIAV envelope sequences observed during sequential febrile episodes produced an increasingly neutralization-resistant phenotype. To further define the envelope determinants of EIAV neutralization specificity, we examined the neutralization properties of a panel of chimeric envelope constructs derived from reciprocal envelope domain exchanges between selected neutralization-sensitive and neutralization-resistant envelope variants. These results indicated that the EIAV gp90 V3 and V4 domains individually conferred serum neutralization resistance while other envelope segments in addition to V3 and V4 were evidently required for conferring total serum neutralization sensitivity. These data clearly demonstrate for the first time the influence of sequential gp90 variation during persistent infection in increasing envelope neutralization resistance, identify the gp90 V3 and V4 domains as the principal determinants of antibody neutralization resistance, and indicate distinct complex cooperative envelope domain interactions in defining sensitivity to serum antibody neutralization.

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Section: Discussionsupporting

confidence: 80%

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Howe¹,

Leroux

Issel

et al. 2002

J Virol

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“…The reduction in the Env-CXCR4 binding capacity induced by DNM is comparable with that observed in conditions that are considered as incompatible with Env/CXCR4 binding (Doranz et al, 1999b). This result further illustrates the influence of Env glycosylation on both its binding to CXCR4 and the mutual interactions between the V1/V2, V3, and C2 domains (Chen et al, 2001). The abnormal immunoreactivity of V1/V2 on Dϩ Env and its altered capacity to interact with CXCR4 and to mediate fusion are also in agreement with studies that highlight the influence of the glycans of the V1/V2 domain in coreceptor usage (Ogert et al, 2001;Pollakis et al, 2001).…”

Section: Dnm and Fusogenicity Of Hiv Env 191supporting

confidence: 87%

The α-Glucosidase Inhibitor 1-Deoxynojirimycin Blocks Human Immunodeficiency Virus Envelope Glycoprotein-Mediated Membrane Fusion at the CXCR4 Binding Step

et al. 2002

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1-Deoxynojirimycin (DNM) is a saccharide decoy that inhibits cellular ␣-glucosidase I-II activity. Treatment by DNM of human immunodeficiency virus (HIV)-infected lymphocyte cultures inhibits virus spread. The functional properties of the membraneassociated Env glycoprotein (Env) modified in the presence of DNM remain unclear because previous reports on this subject have essentially used recombinant soluble Envs whose properties differ notably from those of Env anchored on the surface of the virus. To model virus-associated Env synthesized in the presence of DNM, native Env was expressed at the surface of mammalian cells treated with DNM. As expected, its glycosylation pattern was altered in the presence of the inhibitor. Env was found able to bind CD4, whereas its ability to induce membrane fusion was abolished. The immunoreactivity of regions involved in interactions of Env with CXCR4 (V1, V2, C2, and V3) was modified and Env displayed altered interaction with this coreceptor. These results are consistent with the inhibition by DNM of virus entry at the Env/coreceptor interaction step. Finally, preliminary data indicate that suboptimal concentrations of DNM and natural or synthetic CXCR4 ligands used in combination potently inhibit the Env-mediated membrane fusion process. Altogether, our results suggest that DNM and its analogs deserve further investigation as anti-HIV agents in combination with experimental compounds targeting CXCR4 to inhibit each partner of this crucial step of HIV entry.

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“…Our results show that the T198P mutation reduces 4KG5 binding, consistent with the idea that this mutation may disrupt an interaction between V1/V2 and V3. Indeed, there have been reports suggesting that the V1/V2 loops interact with the V3 loop on the HIV-1 envelope spike (5,7,28) and that carbohydrate may play a role in this interaction (37,55,61). Thus, it is significant that we found a subtle influence of glycans on 4KG5 recognition of gp120 (Fig.…”

mentioning

confidence: 53%

“…Because of their absence in the core gp120 crystal structure, it remains unclear how the V1/V2 and V3 loops spatially relate to one another and to the CD4 and coreceptor binding sites. The nature of the interaction between the V1/V2 and V3 loops has particular relevance to the virus entry process (5,7,26,28,35,39,40,76,89,90). The engagement of the CD4 receptor with gp120 induces the exposure of the cryptic chemokine receptor binding site on gp120, which overlaps the CD4-induced (CD4i) epitope for MAb 17b (64,81,87), as shown in the crystal structure of the gp120 complex (33).…”

mentioning

confidence: 99%

A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12

Zwick

Kelleher

Jensen

et al. 2003

J Virol

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The V1/V2 and V3 loops are proximal to the CD4 binding site (CD4bs) of human immunodeficiency virus type 1 (HIV-1) gp120 and undergo conformational change upon CD4 receptor engagement by the HIV-1 envelope spike. Nearly all of the reported monoclonal antibodies (MAbs) against the CD4bs exhibit a very limited capacity to neutralize HIV-1. However, one such human MAb, immunoglobulin G1 (IgG1) b12, is uniquely able to neutralize primary isolates across subtypes with considerable potency. The molecular basis for the anti-HIV-1 activity of b12 is not fully understood but is relevant to vaccine design. Here we describe a novel human MAb, 4KG5, whose binding to monomeric gp120 is moderately enhanced by IgG1 b12. In sharp contrast, 4KG5 binding to gp120 is inhibited by soluble CD4 (sCD4) and by all other (n ‫؍‬ 14) anti-CD4bs MAbs tested. 4KG5 is unable to recognize gp120 in which either V1, V2, or V3 has been deleted, and MAbs against the V2 or V3 loops inhibit the binding of 4KG5 to gp120. Moreover, 4KG5 is able to inhibit the binding of the CD4-induced MAbs 17b and X5 in the absence of sCD4, whereas 17b and X5 only weakly inhibit the binding of 4KG5 to gp120. Mutagenesis of gp120 provides further evidence of a discontinuous epitope of 4KG5 that is formed by the V1/V2 loop, the V3 loop, and a portion of the bridging sheet (C4). 4KG5 was isolated as a single-chain Fv from a phage display library constructed from the bone marrow of an HIV-1-seropositive subject (FDA2) whose serum neutralizes HIV-1 across subtypes. Despite its source, we observed no significant neutralization with 4KG5 against the autologous (R2) virus and several other strains of HIV-1. The results suggest a model in which antibody access to the CD4bs on the envelope spike of HIV-1 is restricted by the orientation and/or dynamics of the V1/V2 and V3 loops, and b12 avoids these restrictions.

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HIV gp120 V1/V2 and C2-V3 domains glycoprotein compatibility is required for viral replication

Cited by 12 publications

References 44 publications

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

Equine Infectious Anemia Virus Envelope Evolution In Vivo during Persistent Infection Progressively Increases Resistance to In Vitro Serum Antibody Neutralization as a Dominant Phenotype

The α-Glucosidase Inhibitor 1-Deoxynojirimycin Blocks Human Immunodeficiency Virus Envelope Glycoprotein-Mediated Membrane Fusion at the CXCR4 Binding Step

A Novel Human Antibody against Human Immunodeficiency Virus Type 1 gp120 Is V1, V2, and V3 Loop Dependent and Helps Delimit the Epitope of the Broadly Neutralizing Antibody Immunoglobulin G1 b12

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