A Comprehensive Mapping of HIV-1 Genotypes in Various Risk Groups and Regions across China Based on a Nationwide Molecular Epidemiologic Survey

He, Xiang; Xing, Hui; Ruan, Yuhua; Hong, Kui; Cheng, Chonghu; Hu, Yuanyuan; Xin, Ruolei; Wei, Jing; Feng, Yue; Hsi, Jenny H.; Takebe, Yutaka; Shao, Yiming

doi:10.1371/journal.pone.0047289

Cited by 219 publications

(222 citation statements)

References 22 publications

Supporting

Mentioning

197

Contrasting

Order By: Relevance

“…highest prevalence (18,36,37). Why this lineage of viruses was able to spread so rapidly is unclear at the moment; it did not spread particularly rapidly in Africa (14).…”

Section: Discussionmentioning

confidence: 99%

Histidine 375 Modulates CD4 Binding in HIV-1 CRF01_AE Envelope Glycoproteins

Zoubchenok

Veillette

Prévost

et al. 2017

J Virol

View full text Add to dashboard Cite

The envelope glycoproteins (Envs) from human immunodeficiency virus type 1 (HIV-1) mediate viral entry. The binding of the HIV-1 gp120 glycoprotein to CD4 triggers conformational changes in gp120 that allow high-affinity binding to its coreceptors. In contrast to all other Envs from the same phylogenetic group, M, which possess a serine (S) at position 375, those from CRF01_AE strains possess a histidine (H) at this location. This residue is part of the Phe43 cavity, where residue 43 of CD4 (a phenylalanine) engages with gp120. Here we evaluated the functional consequences of replacing this residue in two CRF01_AE Envs (CM244 and 92TH023) by a serine. We observed that reversion of amino acid 375 to a serine (H375S) resulted in a loss of functionality of both CRF01_AE Envs as measured by a dramatic loss in infectivity and ability to mediate cell-to-cell fusion. While no effects on processing or trimer stability of these variants were observed, decreased functionality could be linked to a major defect in CD4 binding induced by the replacement of H375 by a serine. Importantly, mutations of residues 61 (layer 1), 105 and 108 (layer 2), and 474 to 476 (layer 3) of the CRF01_AE gp120 inner domain layers to the consensus residues present in group M restored CD4 binding and wild-type levels of infectivity and cell-to-cell fusion. These results suggest a functional coevolution between the Phe43 cavity and the gp120 inner domain layers. Altogether, our observations describe the functional importance of amino acid 375H in CRF01_AE envelopes.IMPORTANCE A highly conserved serine located at position 375 in group M is replaced by a histidine in CRF01_AE Envs. Here we show that H375 is required for efficient CRF01_AE Env binding to CD4. Moreover, this work suggests that specific residues of the gp120 inner domain layers have coevolved with H375 in order to maintain its ability to mediate viral entry.

show abstract

“…highest prevalence (18,36,37). Why this lineage of viruses was able to spread so rapidly is unclear at the moment; it did not spread particularly rapidly in Africa (14).…”

Section: Discussionmentioning

confidence: 99%

Histidine 375 Modulates CD4 Binding in HIV-1 CRF01_AE Envelope Glycoproteins

Zoubchenok

Veillette

Prévost

et al. 2017

J Virol

View full text Add to dashboard Cite

show abstract

“…Recently, however, MSM is the risk group associated with the most rapid increases in HIV infections within China, and studies note HIV-1 strains of different subtypes and CRFs. [38][39][40][41][42] In cities in northern China CRF01_AE infection in MSM is more common than subtype B, 24,[43][44][45] with similar trends in Beijing, Fujian, Guizho, Guandong, Guanxi, Hebei, Hong Kong, Hunan, Jiangsu, Jianxi, Shanghai, and Yunnan. CRF07_BC has recently been identified in young MSM and in some cities exceeds the prevalence of CRF01_AE infection (unpublished data).…”

Section: Hiv-1 Molecular Epidemiologymentioning

confidence: 91%

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Phanuphak

Shao³

et al. 2015

AIDS Research and Human Retroviruses

Self Cite

View full text Add to dashboard Cite

An overall decrease of HIV prevalence is now observed in several key Asian countries due to effective prevention programs. The decrease in HIV prevalence and incidence may further improve with the scale-up of combination prevention interventions. The implementation of future prevention trials then faces important challenges. The opportunity to identify heterosexual populations at high risk such as female sex workers may rapidly wane. With unabating HIV epidemics among men who have sex with men (MSM) and transgender (TG) populations, an effective vaccine would likely be the only option to turn the epidemic. It is more likely that efficacy trials will occur among MSM and TG because their higher HIV incidence permits smaller and less costly trials. The constantly evolving patterns of HIV-1 diversity in the region suggest close monitoring of the molecular HIV epidemic in potential target populations for HIV vaccine efficacy trials. CRF01_AE remains predominant in southeast Asian countries and MSM populations in China. This relatively steady pattern is conducive to regional efficacy trials, and as efficacy warrants, to regional licensure. While vaccines inducing nonneutralizing antibodies have promise against HIV acquisition, vaccines designed to induce broadly neutralizing antibodies and cell-mediated immune responses of greater breadth and depth in the mucosal compartments should be considered for testing in MSM and TG. The rationale and design of efficacy trials of combination prevention modalities such as HIV vaccine and preexposure prophylaxis (PrEP) remain hypothetical, require high adherence to PrEP, are more costly, and present new regulatory challenges. The prioritization of prevention interventions should be driven by the HIV epidemic and decided by the country-specific health and regulatory authorities. Modeling the impact and cost-benefit may help this decision process.

show abstract

“…Since the first emergence of CRF01_AE HIV-1 strains in Africa and subsequent spread to Asia, where it established a major epidemic, this virus has become the dominant strain in many Asian countries, including southern China and Thailand (48)(49)(50). Why CRF01_AE HIV-1 was able to spread so rapidly is unclear at the moment, but high viral loads and short survival times have been associated with CRF01_AE infection compared with the values seen for HIV-1 infections in the Western world (51)(52)(53).…”

Section: Figmentioning

confidence: 99%

Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses

Prévost

Zoubchenok

Richard

et al. 2017

J Virol

View full text Add to dashboard Cite

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibodydependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid the exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to the CD4-bound state. While residue S375 is well conserved in the majority of group M HIV-1 isolates, CRF01_ AE strains have a naturally occurring histidine at this position (H375). Interestingly, CRF01_AE is the predominant circulating strain in Thailand, where the RV144 trial took place. In this trial, which resulted in a modest degree of protection, ADCC responses were identified as being part of the correlate of protection. Here we investigate the influence of the Phe 43 cavity on ADCC responses. Filling this cavity with a histidine or tryptophan residue in Env with a natural serine residue at this position (S375H/W) increased the susceptibility of HIV-1-infected cells to ADCC. Conversely, the replacement of His 375 by a serine residue (H375S) within HIV-1 CRF01_AE decreased the efficiency of the ADCC response. Our results raise the intriguing possibility that the presence of His 375 in the circulating strain where the RV144 trial was held contributed to the observed vaccine efficacy.

show abstract

A Comprehensive Mapping of HIV-1 Genotypes in Various Risk Groups and Regions across China Based on a Nationwide Molecular Epidemiologic Survey

Cited by 219 publications

References 22 publications

Histidine 375 Modulates CD4 Binding in HIV-1 CRF01_AE Envelope Glycoproteins

Histidine 375 Modulates CD4 Binding in HIV-1 CRF01_AE Envelope Glycoproteins

HIV Epidemic in Asia: Implications for HIV Vaccine and Other Prevention Trials

Influence of the Envelope gp120 Phe 43 Cavity on HIV-1 Sensitivity to Antibody-Dependent Cell-Mediated Cytotoxicity Responses

Contact Info

Product

Resources

About