Genetic factors associated with slow progression of HIV among perinatally-infected Indian children

Chaudhuri, Riya Pal; Neogi, Ujjwal; Rao, Shwetha; Shet, Anita

doi:10.1007/s13312-014-0505-x

Cited by 9 publications

(5 citation statements)

References 15 publications

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“…The HIV disease progression has been shown to be associated with polymorphism in host genes such as HLA, CCR5, SDF-1, KIR, TRIM5α and the ABOBEC3 etc. [38–41]. The V176F polymorphism was not found to be associated with HIV-1 infection which was in the line with the previous reports showing absence of association between this polymorphism (V176F) and HIV infection [10, 18].…”

Section: Discussionsupporting

confidence: 87%

FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

et al. 2019

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BackgroundHIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response.MethodsThe Sanger’s method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed.ResultsTwo polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response.ConclusionThe study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.

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Section: Discussionsupporting

confidence: 87%

FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

et al. 2019

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“…Nearly half of the global HIV infections are caused by the subtype C strain (HIV-1C), which is the most predominant among the nine pure HIV-1 subtypes and numerous unique and circulating recombinant forms (6). In India, approximately 2.1 million people were reported to be living with HIV in the middle of 2017 (UNAIDS global AIDS update, 2017), with more than 99% of infections being caused by HIV-1 subtype C (HIV-1C) strains alone (7)(8)(9)(10)(11). Despite the unique characteristics of HIV-1C, there are considerable differences in the features of viruses within the quasispecies, especially in the transmission efficiency of the virus in vivo.…”

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confidence: 99%

Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses

Ashokkumar

Aralaguppe

Tripathy

et al. 2018

J Virol

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Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7-Luc-IRESs-NefΔgp120 to obtain chimeric viruses. Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection. Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C. The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies. Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants. The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection. CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses. The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection. Tremendous progress has been made during the last three and half decades of HIV research, but some significant gaps continue to exist. One of the frontier areas of HIV research which has not seen a breakthrough yet is vaccine research, which is because of the enormous genetic diversity of HIV-1 and the unique infectious fitness of the virus. Among the repertoire of viral variants, the virus that establishes successful infection (transmitted founder [TF] virus) has not been well characterized yet. An insight into the salient features of the TF virus would go a long way toward helping with the design of an effective vaccine against HIV. Here we studied the biological properties of recently transmitted viruses isolated from infants who acquired infection from the mother and have come up with unique characterizations for the TF virus that establishes infection in the human host.

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“…Several large paediatric LTNP cohorts similar to our cohort have been described in South Africa/Durban , Uganda , Thailand and Cambodia , France and seven other European countries , Brazil , Puerto Rico and the USA . In India, there are limited reports on paediatric LTNP cohorts and analysis of their immune biomarkers .…”

Section: Introductionmentioning

confidence: 62%

“…Since 2010, we have maintained a clinical cohort and sample biorepository of perinatally infected children aged between 1 month and 18 years at St John's Hospital, Bangalore, India . All LTNPs selected for this study had been followed in the cohort for a minimum of 7 years, with at least eight longitudinal consecutive blood samples available up to March 2017 for confirmation of stable CD4 counts.…”

Section: Methodsmentioning

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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Genetic factors associated with slow progression of HIV among perinatally-infected Indian children

Abstract: There is an association between host genetic factors and slow disease progression in this population.

Cited by 9 publications

References 15 publications

FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV

Unique Phenotypic Characteristics of Recently Transmitted HIV-1 Subtype C Envelope Glycoprotein gp120: Use of CXCR6 Coreceptor by Transmitted Founder Viruses

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

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