Comparison of HIV-1 nef and gag Variations and Host HLA Characteristics as Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan Children

Saina, Matilda Chelimo; Bi, Xiuqiong; Lihana, Raphael; Lwembe, Raphael; Ishizaki, Azumi; Panikulam, Annie; Palakudy, Tresa; Musoke, Rachel; Owens, Mary; Songok, Elijah; Ishiguro, Hiroshi

doi:10.1371/journal.pone.0137140

Cited by 4 publications

(6 citation statements)

References 48 publications

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“…found no significant between-group differences in the amino acid variations, insertions, or deletions of gag sequences, and proposed that gag sequence variations are not as important as HLA in influencing disease progression. 25 Inconsistent with this finding, we did observe a significant difference in rate of mutations in the gag gene of the TF group in comparison with those of the TS group, particularly with regard to the PIP2 recognition motif and nucleocapsid basic domains. The PIP2 recognition motif is involved in the assemblance of HIV at the plasma membrane of infected cells, and several studies emphasize the importance of the PIP2 recognition motif for the production of infectious virions, 31 and, without the PIP2 recognition motif, membrane binding would not occur.…”

Section: Discussionsupporting

confidence: 64%

“…24 Saina et al indicated that patients could be either rapid or slow progressors regardless of subtype distribution. 25 In the present study, we found that, even though all patients were found to carry the subtype CRF01_AE, phylogenic cluster analysis reveal that participants belong to different clusters of the phylogenic tree. In addition, Louwagie has suggested that the subtype A has the most diversity of gag gene among other subtypes 26 ; thus, we might speculate that the subtype CRF01_AE might encounter high levels of diversity.…”

Section: Discussionmentioning

confidence: 44%

“…indicated that patients could be either rapid or slow progressors regardless of subtype distribution. 25 …”

Section: Discussionmentioning

confidence: 99%

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Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam

Dang

Pham

Dinh

et al. 2020

Therapeutic Advances in Infection

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Background: Gag protein of human immunodeficiency virus (HIV) has been reported to play a crucial role in establishing infection, viral replication, and disease progression; thus, gag might be related to treatment response. The objective of this study was to investigate molecular genotypes of the gag gene, particularly the important functional binding domains in relation to treatment outcomes. Methods: HIV-infected children enrolled and treated at Vietnam National Children’s Hospital were recruited in the study. A total of 25 gag sequences were generated and used to construct phylogenetic trees and aligned with a reference sequence comparing 17 functional domains. Results: We found that all patients in a treatment failure (TF) group belonged to one cluster of the phylogenetic tree. In addition, the rate of mutations was significantly higher in TF compared with a treatment success (TS) group, specifically the PIP2 recognition motif, and the nucleocapsid basic and zinc motif 2 domains [median and (interquartile range (IQR): 12.5 (6.25–12.5) versus 50 (25–50), p < 0.01; 0 (0–0) versus 0 (0–21.43), p = 0.03 and 0 (0–7.14) versus 7.14 (7.14–7.14), p = 0.04, respectively]. When analyzing gag sequences at different time points in seven patients, we did not observe a consistent mutation pattern related to treatment response. Conclusion: Gag mutations in certain domains might be associated with increased viral load; therefore, studying the molecular genotype of the gag gene might be beneficial in monitoring treatment response in HIV-infected children.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 44%

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Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam

Dang

Pham

Dinh

et al. 2020

Therapeutic Advances in Infection

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“…Acquired immunodeficiency syndrome (AIDS) has been a major public health threat since its discovery in the United States in 1981. In general, the progression from human immunodeficiency virus (HIV) infection to AIDS development takes approximately 8–10 years 1 ; however, this duration varies among individuals. Multiple factors have been found to contribute to the progression of HIV-1 infection, such as immunological, virological and host genetic factors 2 – 6 .…”

Section: Introductionmentioning

confidence: 99%

HIV-1 CRF01_AE strain is associated with faster HIV/AIDS progression in Jiangsu Province, China

Chu

Zhang

et al. 2017

Sci Rep

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The goal of this study was to assess risk factors associated with HIV/AIDS progression. Between May 2007 and December 2014, 114 subjects were enrolled in Wuxi City and examined every 6 months. The pol gene sequence was amplified to ascertain the HIV-1 subtype. A Cox proportional hazards regression model was used to estimate the factors associated with HIV/AIDS progression. The median follow-up time for all 114 subjects was 26.70 months (IQR: 18.50-41.47), while the median progression time of the 38 progressed subjects was 24.80 months (IQR: 14.13-34.38). Overall, the CRF01_AE subtype was correlated with a significant risk of accelerated progression compared to non-CRF01_AE subtypes (HR = 3.14, 95%CI: 1.39-7.08, P = 0.006). In addition, a lower CD4 count (350-499) at baseline was associated with a risk of accelerated HIV/AIDS progression compared to higher CD4 count (≥500) (HR = 4.38, 95%CI: 1.95-9.82, P < 0.001). Furthermore, interaction analyses showed that HIV-1 subtypes interacted multiplicatively with transmission routes or CD4 count at baseline to contribute to HIV/AIDS progression (P = 0.023 and P < 0.001, respectively). In conclusion, the CRF01_AE subtype and a lower CD4 count at baseline tend to be associated with the faster progression of HIV/AIDS. Understanding the factors affecting HIV/AIDS progression is crucial for developing personalized management and clinical counselling strategies.Acquired immunodeficiency syndrome (AIDS) has been a major public health threat since its discovery in the United States in 1981. In general, the progression from human immunodeficiency virus (HIV) infection to AIDS development takes approximately 8-10 years 1 ; however, this duration varies among individuals. Multiple factors have been found to contribute to the progression of HIV-1 infection, such as immunological, virological and host genetic factors [2][3][4][5][6] . In particular, the emergence of RNA sequencing technologies has provided a means for analysing the association between virological factors and HIV/AIDS progression.The HIV-1 subtype has been associated with HIV/AIDS progression and has attracted much interest among researchers [7][8][9][10][11] . Unfortunately, no consensus has been reached in studies exploring the association between subtype and disease progression. Studies conducted in Tanzania and Uganda have suggested that subtype D is correlated with faster rates of CD4+ T-cell decline and disease progression than those observed in other subtypes and recombinant forms of the virus 7,8 . However, a retrospective cohort study conducted during 1996 and 2007 revealed that Africans infected with B clade HIV-1 suffered from faster rates of HIV/AIDS progression compared with those infected with non-B clade subtypes 10 . Furthermore, a meta-analysis demonstrated that the trend of HIV/AIDS progression among different HIV-1 subtypes in a descending order was subtype C > D > AE > G > A 9 . Though numerous prophylactic measures against HIV have been effectively employed in China 12 , they have not been able t...

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“…The factors that determine slow progression in HIV-1 infected individuals are not fully understood, despite extensive studies from many international HIV cohorts [17][18][19]. Several host characteristics and immune and viral mechanisms have been associated with the effective control of the HIV infection [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

People Living with HIV (PLWH) Controllers Induce High Production of IFN-γ to Gag Epitope

Da Silva,

Hildebrando

et al. 2023

Preprint

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We report the characterization of phenotype, genotype, and functional parameters such as CD4+ T cell, viral load, HIV-1 genotype, class I HLA genotype, CCR5 polymorphism, and IFN-γ producing cells from a cohort of 37 people living with HIV-1 (PLWH) (viremic controllers, were compared those on antiretroviral therapy (ART) from two sites in São Paulo, Brazil. Half the PLWH (51.4%) were classified as viremic controllers (Controller group - CG), compared to 48.6% were on ART. As expected, controllers showed baseline higher levels of CD4+ T cells and nadir compared to those under ART, confirming the ability of HIV-1 controllers to preserve these cells even in the absence of ART. IFN-γ-producing cells showed greater magnitude to the HIV peptides Gag in controllers (p<0.03). Our results demonstrated that HLA protective alleles are associated with strong production of IFN-γ to Gag, Nef and RT epitopes in people living with HIV controllers.

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Comparison of HIV-1 nef and gag Variations and Host HLA Characteristics as Determinants of Disease Progression among HIV-1 Vertically Infected Kenyan Children

Cited by 4 publications

References 48 publications

Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam

Molecular genotypes of gag sequences in HIV-1 infected children treated with antiretroviral therapy in Vietnam

HIV-1 CRF01_AE strain is associated with faster HIV/AIDS progression in Jiangsu Province, China

People Living with HIV (PLWH) Controllers Induce High Production of IFN-γ to Gag Epitope

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