Profile of HIV Type 1 Coreceptor Tropism Among Kenyan Patients from 2009 to 2010

Nyamache, Anthony Kebira; Muigai, Anne W. T.; Ng’ang’a, Zipporah; Khamadi, Samoel

doi:10.1089/aid.2012.0284

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…Subtype C for example has been shown to preferentially use CCR5 and to rarely induce syncytia [43, 44]. A few studies involving Kenyan subjects have shown majority of circulating HIV to be R5 tropic, and mostly due to the predominance of R5-tropic HIV subtype A [27, 28, 45]. Significant variations became apparent when tropism is disaggregated by viral subtype, with majority of subtype A1, C and A1 recombinants being R5 tropic.…”

Section: Discussionmentioning

confidence: 99%

Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART

Kitawi

Hunja

Aman

et al. 2017

Virol J

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BackgroundHIV-1 is highly variable genetically and at protein level, a property it uses to subvert antiviral immunity and treatment. The aim of this study was to assess if HIV subtype differences were associated with variations in glycosylation patterns and co-receptor tropism among HAART patients experiencing different virologic treatment outcomes.MethodsA total of 118 HIV env C2V3 sequence isolates generated previously from 59 Kenyan patients receiving highly active antiretroviral therapy (HAART) were examined for tropism and glycosylation patterns. For analysis of Potential N-linked glycosylation sites (PNGs), amino acid sequences generated by the NCBI’s Translate tool were applied to the HIVAlign and the N-glycosite tool within the Los Alamos Database. Viral tropism was assessed using Geno2Pheno (G2P), WebPSSM and Phenoseq platforms as well as using Raymond’s and Esbjörnsson’s rules. Chi square test was used to determine independent variables association and ANOVA applied on scale variables.ResultsAt respective False Positive Rate (FPR) cut-offs of 5% (p = 0.045), 10% (p = 0.016) and 20% (p = 0.005) for CXCR4 usage within the Geno2Pheno platform, HIV-1 subtype and viral tropism were significantly associated in a chi square test. Raymond’s rule (p = 0.024) and WebPSSM (p = 0.05), but not Phenoseq or Esbjörnsson showed significant associations between subtype and tropism. Relative to other platforms used, Raymond’s and Esbjörnsson’s rules showed higher proportions of X4 variants, while WebPSSM resulted in lower proportions of X4 variants across subtypes. The mean glycosylation density differed significantly between subtypes at positions, N277 (p = 0.034), N296 (p = 0.036), N302 (p = 0.034) and N366 (p = 0.004), with HIV-1D most heavily glycosylated of the subtypes. R5 isolates had fewer PNGs than X4 isolates, but these differences were not significant except at position N262 (p = 0.040). Cell-associated isolates from virologic treatment success subjects were more glycosylated than cell-free isolates from virologic treatment failures both for the NXT (p = 0.016), and for all the patterns (p = 0.011).ConclusionThese data reveal significant associations of HIV-1 subtype diversity, viral co-receptor tropism, viral suppression and envelope glycosylation. These associations have important implications for designing therapy and vaccines against HIV. Heavy glycosylation and preference for CXCR4 usage of HIV-1D may explain rapid disease progression in patients infected with these strains.

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Section: Discussionmentioning

confidence: 99%

Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART

Kitawi

Hunja

Aman

et al. 2017

Virol J

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“…Additionally, there is also some correlation with HIV-1 genetic variants. R5 viruses are more often detected in subtype A, regardless of the stage of the disease [20], [21], [22].…”

Section: Introductionmentioning

confidence: 99%

HIV Coreceptors Related Genes (CCR5 and CXCR4) Promoter Methylation: Original Research

Esman,

Salamaikina,

Vinokurov

et al. 2024

Preprint

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The persistence of human immunodeficiency virus (HIV) in viral reservoirs is a topical issue. There are many factors that can potentially influence this process. Epigenetic alterations according to the literature could be such factors. In this study, we present a detailed description of gene promoters research and development techniques for determining the methylation level of CpG loci in these promoters based on Sanger sequencing and pyrosequencing. The presented methods could be used for measuring the methylation levels in other research.A total of 51 samples of biological material from 17 patients at three visits were used in this study. Applying the developed techniques, we found that the CpG loci of theCXCR4gene promoter were not methylated. For CpG loci of theCCR5gene promoter no change in methylation levels was observed visit to visit. CpG 1 methylation level ranged from 33% to 53%, CpG 2 - from 4.4% to 11%, CpG 3 - from 0 to 42% and CpG 4 - from 1% to 21%. These values were derived from measurements of C-peaks in sequences.Key ContributionThe breakthroughs or highlights of the manuscript. Authors can write one or two sentences to describe the most important part of the paper.

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“…8 A strong selection for viral variants using CCR5 as a coreceptor occurs during transmission, as most children are infected with R5 viruses. [9][10][11][12] Prevention of mother-to-child transmission (PMTCT) of HIV-1 is one of the key components of the worldwide response to the pandemic and is based on the prophylactic use of antiretroviral drugs (ARVs). In developed countries, MTCT of HIV-1 has been reduced to less than 2% by combination antiretroviral therapy (ART), selective caesarian delivery, and avoidance of breastfeeding.…”

Section: Introductionmentioning

confidence: 99%

Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam

Phan

Pham

et al. 2015

AIDS Research and Human Retroviruses

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We previously reported mother-to-child transmission of HIV-1 in nine (6.7%) of 135 children on nevirapine prophylaxis in Vietnam. In the current study, we investigated the appearance and profile of antiretroviral drug (ARV) resistance mutations, the predicted coreceptor usage, and the genetic diversity of HIV-1 strains isolated from the eight pairs of HIV-1-infected mothers and their children, who were followed up to 12 months after birth. Portions of the pol and env C2V3 regions of the HIV-1 strains were analyzed genetically. HIV-1 CRF01_AE RNA was detected in four (50%) children at delivery. Y181C, a nevirapine resistance mutation, appeared in two (25%) children 1 and 3 months after birth, respectively. No ARV resistance mutation was detected in the mothers, though three mothers were on ARV prophylaxis. Five mothers and their children harbored CCR5-tropic (R5) viruses. Two mothers harbored both R5 and CXCR4-tropic (X4) viruses, but their children harbored only R5 viruses even though the X4 viruses were dominant in the mothers. In the remaining one mother, HIV-1 RNA was not amplified and her child harbored both R5 and X4 viruses at birth, but only X4 virus 12 months after delivery. The infants' viruses were more homogeneous than their mothers' viruses (mean distance: 0.5% vs.

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Profile of HIV Type 1 Coreceptor Tropism Among Kenyan Patients from 2009 to 2010

Cited by 5 publications

References 30 publications

Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART

Partial HIV C2V3 envelope sequence analysis reveals association of coreceptor tropism, envelope glycosylation and viral genotypic variability among Kenyan patients on HAART

HIV Coreceptors Related Genes (CCR5 and CXCR4) Promoter Methylation: Original Research

Genetic Analyses of HIV-1 Strains Transmitted from Mother to Child in Northern Vietnam

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