Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility

Walter, Brandon L.; Armitage, Andrew E.; Graham, Stephen C.; Oliveira, Túlio de; Skinhøj, Peter; Jones, E Y; Stuart, David I.; McMichael, Andrew J.; Chesebro, Bruce; Iversen, Astrid K. N.

doi:10.1097/qad.0b013e32832a1806

Cited by 21 publications

(16 citation statements)

References 53 publications

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“…The HIV epidemic in India is attributed mainly to HIV‐1 subtype C, the viral clade that accounts for approximately half of all global infections . Multiple lines of evidence suggest that subtype C may have greater replicative fitness than other subtypes , with a greater magnitude of transcription and high transmissibility .…”

Section: Introductionmentioning

confidence: 99%

Increased monocyte activation with age among HIV‐infected long term non‐progressor children: implications for early treatment initiation

D'Souza

Gopalan

Rajnala³

et al. 2019

HIV Medicine

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Objectives The key to newer therapeutic and eradication approaches often lies in understanding slow disease progression in HIV infection. The paediatric population has been poorly studied in this regard. We aimed to describe a cohort of perinatally infected long‐term nonprogressor (LTNP) children living with HIV in India and to evaluate the immune biomarkers of disease progression. Methods LTNPs (ART‐naïve, with a CD4 count ≥ 500 cells/μL at age ≥ 7 years) among the cohort of HIV‐infected children were identified and monitored longitudinally, and their CD4 T‐cell counts and plasma viral loads were measured every 6 months. The plasma monocyte/macrophage activation markers, namely soluble CD14 (sCD14), soluble CD163 (sCD163) and interferon‐inducible protein‐10 (IP‐10) were measured by enzyme‐linked immunosorbent assay (ELISA) in LTNPs and progressors. The Mann–Whitney U‐test was used to compare the two groups and P values < 0.05 were considered statistically significant. Spearman's rank or Pearson's correlation coefficient (r) was calculated to determine the associations between variables. Results Among 378 children living with HIV‐1 surveyed in our cohort, 40 (10.6%) were LTNPs. Longitudinal analysis of the LTNP data showed that both CD4 count and viral load declined significantly with age (P < 0.0001 for both). Plasma sCD14 levels were significantly (P < 0.005) higher in progressors and sCD163 levels were significantly (P < 0.0001) higher in LTNPs. Conclusions The prevalence of LTNPs in our cohort of perinatally infected children living with HIV was 10.6%. We observed a trend for associations between the increasing sCD163 monocyte/macrophage activation marker levels, declining CD4 counts and the gradual loss of nonprogressor status with age in the LTNPs. These findings underscore the need for early antiretroviral therapy in those children with proven slow disease progression.

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Section: Introductionmentioning

confidence: 99%

Increased monocyte activation with age among HIV‐infected long term non‐progressor children: implications for early treatment initiation

D'Souza

Gopalan

Rajnala³

et al. 2019

HIV Medicine

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“…Given this diversity, it is not surprising that natural (patient-derived) HIV-1 sequences also exhibit differences in their in vitro function, which may in turn influence viral pathogenesis. For example, it has been hypothesized that HIV-1 subtype C isolates, which comprise more than >50% of infections worldwide (Hemelaar, 2012), may be inherently more transmissible - possibly because of subtype-specific motifs within Env-gp120 that modulate interactions with host cell entry receptors (Walter et al, 2009) - though this remains controversial (Kahle et al, 2014). Subtype-specific differences in HIV-1 entry efficiency (Marozsan et al, 2005), replication capacity (Aralaguppe et al, 2016; Konings et al, 2006), and the function of viral accessory proteins Vif (Binka et al, 2012; Iwabu et al, 2010) and Nef (Mann et al, 2013) have also been described.…”

Section: Introductionmentioning

confidence: 99%

In vitro functional assessment of natural HIV-1 group M Vpu sequences using a universal priming approach

Rahimi

Anmole

Soto-Nava³

et al. 2017

Journal of Virological Methods

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The HIV-1 accessory protein Vpu exhibits high inter- and intra- subtype genetic diversity that may influence Vpu function and possibly contribute to HIV-1 pathogenesis. However, scalable methods to evaluate genotype/phenotype relationships in natural Vpu sequences are limited, particularly those expressing the protein in CD4+ T-cells, the natural target of HIV-1 infection. A major impediment to assay scalability is the extensive genetic diversity within, and immediately upstream of, Vpu's initial 5' coding region, which has necessitated the design of oligonucleotide primers specific for each individual HIV-1 isolate (or subtype). To address this, we developed two universal forward primers, located in relatively conserved regions 38 and 90 bases upstream of Vpu, and a single universal reverse primer downstream of Vpu, which are predicted to cover the vast majority of global HIV-1 group M sequence diversity. We show that inclusion of up to 90 upstream bases of HIV-1 genomic sequence does not significantly influence in vitro Vpu expression or function when a Rev/Rev Response Element (RRE)-dependent expression system is used. We further assess the function of four diverse HIV-1 Vpu sequences, revealing reproducible and significant differences between them. Our approach represents a scalable option to measure the in vitro function of genetically diverse natural Vpu isolates in a CD4+ T-cell line.

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“…The explosion of heterosexually transmitted HIV-1 throughout southern Africa in the 1990s was almost exclusively due to HIV-1 subtype C, leading some to hypothesize that subtype C might be more transmissible compared to other subtypes 3–6 . Laboratory studies have suggested molecular and genetic characteristics of subtype C that could promote more efficient transmission 7–9 . However, clear evidence for differential transmissibility of HIV-1 subtypes in population-level epidemiological studies has not been shown 10–12 .…”

Section: Introductionmentioning

confidence: 99%

HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission

Kahle¹,

Campbell²,

Lingappa

et al. 2014

Aids

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Background HIV-1 subtype C has emerged as the most prevalent strain of HIV-1 worldwide, leading to speculation that subtype C may be more transmissible than other subtypes. We compared the risk of HIV-1 transmission for subtype C versus non-C subtypes (A, D, G and recombinant forms) among heterosexual African HIV-1 serodiscordant couples. Methods We conducted a nested case-control analysis using data from two prospective cohort studies of heterosexual HIV-1 serodiscordant couples from 6 countries in eastern and southern Africa. Cases (N=121) included incident HIV-1 transmissions that were established as linked within the serodiscordant partnership by viral sequencing; controls (N=501) were non-transmitting HIV-1 infected partners. Subtype was determined for partial env and gag genes. Multiple logistic regression controlled for age and gender of the HIV-1 infected partner and self-reported unprotected sex. Plasma and genital HIV-1 RNA concentrations were compared between subtype C and non-C subtypes using generalized estimating equations. Results HIV-1 subtype C was not associated with increased risk of HIV-1 transmission compared to non-C subtypes: env adjusted odds ratio (adjOR) 1.14 (95% confidence interval [CI] 0.74–1.75, p=0.6) and gag adjOR 0.98 (95% CI 0.63–1.52, p=0.9). Plasma and genital HIV-1 RNA levels did not differ significantly for subtype C versus non-C. Conclusion In a geographically diverse population of heterosexual African HIV-1 serodiscordant couples, subtype C was not associated with greater risk of HIV-1 transmission compared to non-C subtypes, arguing against the hypothesis that subtype C is more transmissible compared to other common subtypes.

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Functional characteristics of HIV-1 subtype C compatible with increased heterosexual transmissibility

Abstract: Background-Despite the existence of over 50 subtypes and circulating recombinant forms of human immunodeficiency virus type-1 (HIV-1), subtype-C dominates the heterosexual pandemic causing 56% of all infections.

Cited by 21 publications

References 53 publications

Increased monocyte activation with age among HIV‐infected long term non‐progressor children: implications for early treatment initiation

Increased monocyte activation with age among HIV‐infected long term non‐progressor children: implications for early treatment initiation

In vitro functional assessment of natural HIV-1 group M Vpu sequences using a universal priming approach

HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission

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