| 1. |
- Barathan, Muttiah, et al.
(author)
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CD8+T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides
- 2017
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In: Cellular Immunology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0008-8749 .- 1090-2163. ; 313
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Journal article (peer-reviewed)abstract
- Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray (TM) following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-beta 1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-alpha, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence. (C) 2016 Elsevier Inc. All rights reserved.
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| 2. |
- Barathan, Muttiah, et al.
(author)
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Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes
- 2015
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In: Apoptosis (London). - : Springer Verlag (Germany). - 1360-8185 .- 1573-675X. ; 20:4, s. 466-480
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Journal article (peer-reviewed)abstract
- Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(A (R)) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.
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| 3. |
- Selvavinayagam, Sivaprakasam T., et al.
(author)
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Clinical characteristics and novel mutations of omicron subvariant XBB in Tamil Nadu, India - a cohort study
- 2023
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In: The Lancet Regional Health - Southeast Asia. - : ELSEVIER. - 2772-3682. ; 19
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Journal article (peer-reviewed)abstract
- Background Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India. Methods Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients. Findings Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population. Interpretation Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants.Funding National Health Mission (India), SIDA SARC, VINNMER (Sweden), ORIP/NIH (USA).Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 4. |
- Selvavinayagam, Sivaprakasam T., et al.
(author)
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Evolution of the Omicron B.1.1.529 Sars-Cov-2 and its Variants in Tamil Nadu, India – a State-Wide Prospective Longitudinal Genomic Surveillance
- 2023
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Other publication (other academic/artistic)abstract
- Background: The emergence of the omicron SARS-CoV-2 variant beholding many mutations, especially in the spike (S) protein severely threatens global health. With an aim to understand the mutational pattern of the variant and its genetic interrelationship in the Indian population, here we prospectively followed the viral evolution and transmission between December 2021 and March 2023 in Tamil Nadu.Methods: A total of 11526 nasopharyngeal and oropharyngeal swabs (6431 males, 5095 females including 603 children) collected from across the 38 districts of Tamil Nadu were subjected to WGS. Of the 10663 samples (92.5%) positive for omicron variants, 1688 were sequenced at the State Public Health Laboratory. We longitudinally studied the evolutionary dynamics of the different omicron variants, starting from the first detected case (B.1.1.529) to the recently reported recombinant XBB variants by sequencing the S gene and by performing phylo-geographic and molecular modeling analyses.Findings: Administration of a booster dose was associated with reduced risk of hospitalization and death. BA.1 sub-variants and BA.2.75 were associated with increased risk of severe disease, whereas BA.1 and BA.2 were associated with increased risk of death. High quality WGS data from 150 samples revealed six major omicron clusters and several other sub-clusters. Seven variants in the same BA lineages with different divergences in the S protein were noticed. Of the 5009 mutations detected, the highest was seen in the receptor-binding domain (RBD) followed by the N-terminal domain (NTD) in varying proportions among the different omicron lineages. Importantly, the mutations were observed in the sub-domain (SD1/2) furin cleavage site, fusion peptide (FP), and the heptapeptide repeat sequence (HR1) regions. Notably, unique mutations Y473I, P479F, C480F, V483T, E484C, G485T, P491G, L492K, S494M, Y495C, and G496Q were detected in BA.2.43 whereas A475Q and T478S occurred in the RBD domain of the BA.2.43 variant. The XBB variant showed 41 different mutations between the HR1 and HR2 domains of the S2 subunit. Molecular modeling using BA.2 lineage as a template for seven divergent proteins showed that BA.2.12.1, BA.4 and BA.5 exhibited strong binding affinity towards ACE2.Interpretation: The high frequency of mutations in the RBD highlights the wider distribution of vaccine escape-variants that would impact the structural and functional attributes of the omicron variant in the population. Further, our work provides key insights on the evolutionary pattern leading to the identification of seven divergent variants of omicron in Tamil Nadu, India.
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| 5. |
- Selvavinayagam, Sivaprakasam T., et al.
(author)
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Genomic surveillance of omicron B.1.1.529 SARS‐CoV‐2 and its variants between December 2021 and March 2023 in Tamil Nadu, India—A state‐wide prospective longitudinal study
- 2024
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In: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
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Journal article (peer-reviewed)abstract
- A state-wide prospective longitudinal investigation of the genomic surveillance of the omicron B.1.1.529 SARS-CoV-2 variant and its sublineages in Tamil Nadu, India, was conducted between December 2021 and March 2023. The study aimed to elucidate their mutational patterns and their genetic interrelationship in the Indian population. The study identified several unique mutations at different time-points, which likely could attribute to the changing disease characteristics, transmission, and pathogenicity attributes of omicron variants. The study found that the omicron variant is highly competent in its mutating potentials, and that it continues to evolve in the general population, likely escaping from natural as well as vaccine-induced immune responses. Our findings suggest that continuous surveillance of viral variants at the global scenario is warranted to undertake intervention measures against potentially precarious SARS-CoV-2 variants and their evolution.
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| 6. |
- Selvavinayagam, Sivaprakasam T, et al.
(author)
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Plasma CXCL8 and MCP-1 as biomarkers of latent tuberculosis infection
- 2023
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Other publication (other academic/artistic)abstract
- BackgroundEarly detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy.Methods We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay.ResultsIncreased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold.ConclusionsWe postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.
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| 7. |
- Selvavinayagam, Sivaprakasam T, et al.
(author)
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Plasma CXCL8 and MCP-1 as surrogate plasma biomarkers of latent tuberculosis infection among household contacts-A cross-sectional study
- 2023
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In: PLOS Global Public Health. - : Public Library of Science (PLoS). - 2767-3375. ; 3:11
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Journal article (peer-reviewed)abstract
- Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-a, and IFN-? were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.
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| 8. |
- Shankar, Esaki M., et al.
(author)
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HIV-Mycobacterium tuberculosis co-infection: a `danger-couplemodel of disease pathogenesis
- 2014
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In: PATHOGENS AND DISEASE. - : Wiley / Blackwell Publishing Ltd. - 2049-632X. ; 70:2, s. 110-118
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Research review (peer-reviewed)abstract
- Tuberculosis (TB) and human immunodeficiency virus (HIV) infection interfere and impact the pathogenesis phenomena of each other. Owing to atypical clinical presentations and diagnostic complications, HIV/TB co-infection continues to be a menace for healthcare providers. Although the increased access to highly active antiretroviral therapy (HAART) has led to a reduction in HIV-associated opportunistic infections and mortality, the concurrent management of HIV/TB co-infection remains a challenge owing to adverse effects, complex drug interactions, overlapping toxicities and tuberculosis -associated immune reconstitution inflammatory syndrome. Several hypotheses have been put forward for the exacerbation of tuberculosis by HIV and vice versa supported by immunological studies. Discussion on the mechanisms produced by infectious cofactors with impact on disease pathology could shed light on how to design potential interventions that could decelerate disease progression. With no vaccine for HIV and lack of an effective vaccine for tuberculosis, it is essential to design strategies against HIV–TB co-infection.
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| 9. |
- Shankar, Esaki M., et al.
(author)
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Understanding Immune Senescence, Exhaustion, and Immune Activation in HIV–Tuberculosis Coinfection
- 2017
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In: Handbook of Immunosenescence: Basic Understanding and Clinical Implications. - Cham : Springer. - 9783319645971 ; , s. 1-15
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Book chapter (peer-reviewed)abstract
- Human immunodeficiency virus (HIV) and tuberculosis (TB) coinfection accounts for high rates of global morbidity and mortality. Although the pathogeneses of HIV and Mycobacterium tuberculosis (MTB) infections are different, the coexistence of both the agents will lead to accentuated disease progression in the host. Expression of markers associated with chronic immune activation, exhaustion, and immunosenescence on pathogen-specific CD4+ and CD8+ T cells have been associated with suboptimal immune responses in HIV–TB coinfection. The effect of chronic immune activation, exhaustion, and immunosenescence also appears to extend across distinct sets of immune cells, and hence a wider understanding of the mechanistic aspects underlying these phenomena is urgently required to necessitate the expansion of immune cells with improved functions in HIV–TB coinfection. Furthermore, strategies to cause attrition of immunosenescence and immune activation appear to stem from an improved understanding of senescence signaling.
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| 10. |
- Vignesh, Ramachandran, et al.
(author)
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Gut Microbiota Peculiarities in Aged HIV-Infected Individuals : Molecular Understanding and Therapeutic Perspectives
- 2023
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In: Gut Microbiota in Aging and Chronic Diseases. - Cham : Springer. - 9783031140228 - 9783031140235 ; , s. 415-439
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Book chapter (peer-reviewed)abstract
- Aging is a progressive physiological process that involves alterations in the population of normal gutGut microbiotaGut microbiota. HIV infectionHIV infection in conjunction with agingAgeing complicates the quality of immune responses paving way for increased epithelial permeability and translocation of commensals and pathogen-derived substances into the systemic circulation. Enteric dysbiosisDysbiosis is linked with other comorbidities of agingAging including cardiovascular diseases and dementia in the HIV-infected population. The diversity of gutGut microbiotaGut microbiota declines with ageAge, and HIV infectionHIV infection compromises the effective functioning of the immune system complicating the metabolic as well as regulatory programming of the host’s physiological machinery. Given the scenario of the global HIV/AIDS and the COVID-19 pandemics, it is also likely that alterations in gutGut microbiotaGut microbiota potentially could contribute to post-acute COVID-19 syndrome as well as accelerate the rate of HIV disease progression. The current chapter discusses the role of normal gutGut microbiotaGut microbiota in the aged HIV-infected population and their functional implications in normal cellular and molecular mechanisms in the host.
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