Structure of an HIV-2 gp120 in Complex with CD4

Davenport, Yunji W.; West, Anthony P.; Björkman, Pamela J.

doi:10.1128/jvi.02678-15

Cited by 18 publications

(21 citation statements)

References 46 publications

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“…The differences between the slower and faster progressors with respect to positive selection at conserved sites were most highly pronounced in the C2 region (12 versus 3 sites, respectively) ( P = 0.021 [FET]), while such differences were not observed in the V1V2, V3, and C3 regions. To confirm previous observations that C2 is well exposed on the HIV-2 env gene, we used the published structural data of HIV-2 gp125 to visualize the amino acids in the V1-C3 region (24, 26). This analysis indicated that the majority (15 of 22) amino acids associated with positive selection mapped to exposed surfaces on HIV-2 gp125 (see Fig.…”

Section: Resultsmentioning

confidence: 94%

Low Postseroconversion CD4 ⁺ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Palm

Lemey

Jansson

et al. 2019

mBio

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The relationship between HIV evolution and disease progression is fundamental to our understanding of HIV immune control and vaccine design. There are no clear definitions for faster and slower HIV-2 disease progression and for the relationship of the rate of progression with HIV-2 evolution. To address the hypothesis that viral evolution is correlated with disease progression in HIV-2 infection, we determined faster and slower disease progression based on follow-up data from a prospective cohort of police officers in Guinea-Bissau. The analysis showed that although the CD4+ T-cell level and the decline in the level were independently associated with progression to AIDS, only the CD4+ T-cell level or a combined CD4+ T-cell level/decline stratification was associated with the rate of HIV-2 evolution. The HIV-2 evolutionary rate was almost twice as high among the faster progressors as among the slower progressors. Importantly, this report defines previously unknown characteristics linking HIV-2 disease progression with virus evolution.

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Section: Resultsmentioning

confidence: 94%

Low Postseroconversion CD4 ⁺ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Palm

Lemey

Jansson

et al. 2019

mBio

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“…The Env protein complex mediates attachment to and entry into target cells first through recognition of CD4 + initiating a cascade of conformation reorganization of the Env protein complex that ultimately leads to the fusion of the viral envelope with the host cellular membrane and infection ( Fig. 2 D) ( Jones et al., 1998 , Davenport et al., 2015 ). Lectins are considered HIV entry inhibitors as they interact with the glycosylation moieties of the Env protein complex preventing the conformational rearrangements required for viral fusion ( Barrientos et al., 2006 ).…”

Section: Molecular Mechanisms Of Antiviral Lectinsmentioning

confidence: 99%

Antiviral lectins: Selective inhibitors of viral entry

2017

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Many natural lectins have been reported to have antiviral activity. As some of these have been put forward as potential development candidates for preventing or treating viral infections, we have set out in this review to survey the literature on antiviral lectins. The review groups lectins by structural class and class of source organism we also detail their carbohydrate specificity and their reported antiviral activities. The review concludes with a brief discussion of several of the pertinent hurdles that heterologous proteins must clear to be useful clinical candidates and cites examples where such studies have been reported for antiviral lectins. Though the clearest path currently being followed is the use of antiviral lectins as anti-HIV microbicides via topical mucosal administration, some investigators have also found systemic efficacy against acute infections following subcutaneous administration.

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“…This finding would be supported by the hypothesized open structure of the HIV-2 V3 loop, which might reduce the role of interactions among the amino acids in the V3 loop [27]. Determining and analyzing the structure of gp125 with an intact and ordered V3 loop would be a crucial step in confirming the independence of positions by elucidating the accessibility of the V3 loop [50]. …”

Section: Discussionmentioning

confidence: 99%

A genotypic method for determining HIV-2 coreceptor usage enables epidemiological studies and clinical decision support

et al. 2016

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BackgroundCCR5-coreceptor antagonists can be used for treating HIV-2 infected individuals. Before initiating treatment with coreceptor antagonists, viral coreceptor usage should be determined to ensure that the virus can use only the CCR5 coreceptor (R5) and cannot evade the drug by using the CXCR4 coreceptor (X4-capable). However, until now, no online tool for the genotypic identification of HIV-2 coreceptor usage had been available. Furthermore, there is a lack of knowledge on the determinants of HIV-2 coreceptor usage. Therefore, we developed a data-driven web service for the prediction of HIV-2 coreceptor usage from the V3 loop of the HIV-2 glycoprotein and used the tool to identify novel discriminatory features of X4-capable variants.ResultsUsing 10 runs of tenfold cross validation, we selected a linear support vector machine (SVM) as the model for geno2pheno[coreceptor-hiv2], because it outperformed the other SVMs with an area under the ROC curve (AUC) of 0.95. We found that SVMs were highly accurate in identifying HIV-2 coreceptor usage, attaining sensitivities of 73.5% and specificities of 96% during tenfold nested cross validation. The predictive performance of SVMs was not significantly different (p value 0.37) from an existing rules-based approach. Moreover, geno2pheno[coreceptor-hiv2] achieved a predictive accuracy of 100% and outperformed the existing approach on an independent data set containing nine new isolates with corresponding phenotypic measurements of coreceptor usage. geno2pheno[coreceptor-hiv2] could not only reproduce the established markers of CXCR4-usage, but also revealed novel markers: the substitutions 27K, 15G, and 8S were significantly predictive of CXCR4 usage. Furthermore, SVMs trained on the amino-acid sequences of the V1 and V2 loops were also quite accurate in predicting coreceptor usage (AUCs of 0.84 and 0.65, respectively).ConclusionsIn this study, we developed geno2pheno[coreceptor-hiv2], the first online tool for the prediction of HIV-2 coreceptor usage from the V3 loop. Using our method, we identified novel amino-acid markers of X4-capable variants in the V3 loop and found that HIV-2 coreceptor usage is also influenced by the V1/V2 region. The tool can aid clinicians in deciding whether coreceptor antagonists such as maraviroc are a treatment option and enables epidemiological studies investigating HIV-2 coreceptor usage. geno2pheno[coreceptor-hiv2] is freely available at http://coreceptor-hiv2.geno2pheno.org.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0320-7) contains supplementary material, which is available to authorized users.

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Structure of an HIV-2 gp120 in Complex with CD4

Cited by 18 publications

References 46 publications

Low Postseroconversion CD4 ⁺ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Low Postseroconversion CD4 ⁺ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Antiviral lectins: Selective inhibitors of viral entry

A genotypic method for determining HIV-2 coreceptor usage enables epidemiological studies and clinical decision support

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Structure of an HIV-2 gp120 in Complex with CD4

Cited by 18 publications

References 46 publications

Low Postseroconversion CD4 + T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Low Postseroconversion CD4 + T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Antiviral lectins: Selective inhibitors of viral entry

A genotypic method for determining HIV-2 coreceptor usage enables epidemiological studies and clinical decision support

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Product

Resources

About

Low Postseroconversion CD4 ⁺ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Low Postseroconversion CD4 ⁺ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection