High replication fitness and transmission efficiency of HIV-1 subtype C from India: Implications for subtype C predominance

Rodriguez, Milka A.; Ding, Ming; Ratner, Deena; Chen, Yue; Tripathy, Srikanth; Kulkarni, Smita; Chatterjee, Ramdas; Tarwater, Patrick M.; Gupta, Phalguni

doi:10.1016/j.virol.2008.12.025

Cited by 37 publications

(36 citation statements)

References 36 publications

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“…[54][55][56] A breakdown of HIV-1 in Yunnan includes CRF07_BC (18.9%), CRF08_BC (39.1%), and CRF01_AE (22.4%) 57 ; pol sequences in newly diagnosed HIV-infected individuals from Dehong county, Yunnan, showed that subtype C accounted for 43.1%, URF for 18.4%, CRF01_AE for 17.7%, B for 10.7%, CRF08_BC for 8.4%, and CRF07_BC for 1.7% 58 ; near-full-genome sequencing results show that many new CRFs have been generated in this region. [59][60][61][62] In India, subtype C is the predominant circulating subtype, [63][64][65][66] irrespective of the route of transmission, 67,68 and has been reported as one of the parental strains of CRF07_BC and CRF08_BC in China. 69 URFs of subtype C with B¢ are increasing, especially in the northeastern states.…”

Section: Hiv-1 Molecular Epidemiologymentioning

confidence: 99%

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

Phanuphak

Shao³

et al. 2015

AIDS Research and Human Retroviruses

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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.

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Section: Hiv-1 Molecular Epidemiologymentioning

confidence: 99%

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

Phanuphak

Shao³

et al. 2015

AIDS Research and Human Retroviruses

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“…There are conflicting reports regarding the rate of disease progression of subtype C relative to that of other subtypes (12,(15)(16)(17)(18). While there is general agreement that subtype C has a transmissibility rate at least equal to those of other M group subtypes (19,20), some studies have reported increased transmissibility of subtype C compared to subtypes A and D (21)(22)(23). Furthermore, the higher heterosexual transmission of subtype A than of subtype D (24) may have contributed to the expansion of subtype A in Uganda (9).…”

mentioning

confidence: 99%

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Kiguoya

Mann

Chopera

et al. 2017

J Virol

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There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication, and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates (r ϭ 0.51; P ϭ 0.04), indicating that Gag-protease is a significant contributor to viral replication capacity. Furthermore, we investigated subtype-specific differences in Gag-proteasedriven replication capacity using large well-characterized cohorts in Africa and the Americas. Patient-derived Gag-protease sequences were inserted into an HIV-1 NL4-3 backbone, and the replication capacities of the resulting recombinant viruses were measured in an HIV-1-inducible reporter T cell line by flow cytometry. Recombinant viruses expressing subtype C Gag-proteases exhibited substantially lower replication capacities than those expressing subtype B Gag-proteases (P Ͻ 0.0001); this observation remained consistent when representative Gag-protease sequences were engineered into an HIV-1 subtype C backbone. We identified Gag residues 483 and 484, located within the Alix-binding motif involved in virus budding, as major contributors to subtype-specific replicative differences. In East African cohorts, we observed a hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C Ͻ D Ͻ intersubtype recombinants (P Ͻ 0.0029), which is consistent with reported intersubtype differences in disease progression. We thus hypothesize that the lower Gagprotease-driven replication capacity of subtypes A and C slows disease progression in individuals infected with these subtypes, which in turn leads to greater opportunity for transmission and thus increased prevalence of these subtypes.IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there are reported differences in their rates of disease progression and epidemic spread. The biological determinants underlying these differences have not been fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication capacity correlates with Citation Kiguoya MW, Mann JK, Chopera D, Gounder K, Lee GQ, Hunt PW, Martin JN, Ball TB, Kimani J, Brumme ZL, Brockman MA, Ndung'u T. 2017. Subtype-specific differences in Gagprotease-driven replication capacity are consistent with intersubtype differences in HIV-1 disease progression. J Virol 91:e00253-17.

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“…The in vitro replication fitness and transmission efficiency of primary isolates of HIV-1 subtypes C was higher than subtype A primary isolates [34]. This probably explains the predominance of subtype C strains in spite of introduction of subtype A strains in India more than decade and half ago.…”

Section: Indian Hiv Strainsmentioning

confidence: 95%