| 1. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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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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Annan publikation (övrigt vetenskapligt/konstnärligt)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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| 2. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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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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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Selvavinayagam, Sivaprakasam T, et al.
(författare)
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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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Ingår i: PLOS Global Public Health. - : Public Library of Science (PLoS). - 2767-3375. ; 3:11
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Platelet-Large Cell Ratio and Erythrocyte Sedimentation Rate are Surrogate Predictors of Latent Tuberculosis Infection
- 2024
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aims: Prompt detection and treatment of latent tuberculosis infection (LTBI) holds the key to global TB elimination. The lack of an established test for predicting LTBI poses a substantial challenge in disease management. Here, we identified the biochemical and hematological markers of LTBI, and correlated their usefulness to discriminate LTBI from healthy controls. Main Methods: We conducted a cross-sectional investigation and correlated the various biochemical and hematological markers for detecting LTBI among household contacts (HHCs) of TB infection. Our study included 90 individuals – 30 healthy controls, 30 interferon-gamma release assay (IGRA) positive HHCs, and 30 IGRA-negative HHCs. Biomarkers were measured using designated auto analyzers. Key Findings: ESR, MPV, D-dimer, P-LCR, and PDW were significantly higher among LTBI subjects. ESR, PDW, and P-LCR were markedly associated with LTBI. Multivariate analysis showed that either ESR or P-LCR greater than their respective predetermined cut-off values showed higher odds of developing LTBI. Our study demonstrated that ESR and P-LCR are good surrogate markers for diagnosing LTBI. Also, significantly low ferritin in females and MCHC in males belonging to the HHC/IGRA-ve were observed. Significance: The ESR and P-LCR could aid in predicting LTBI among HHCs. Further, the low serum ferritin is associated with TB resisters.
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| 5. |
- Vignesh, Ramachandran, et al.
(författare)
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Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome-An Extempore Game of Misfiring with Defense Arsenals
- 2023
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Ingår i: Pathogens. - : MDPI. - 2076-0817. ; 12:2
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Forskningsöversikt (refereegranskat)abstract
- The lethal combination involving TB and HIV, known as "syndemic" diseases, synergistically act upon one another to magnify the disease burden. Individuals on anti-retroviral therapy (ART) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART, eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although a significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic marker still remain a grey area of investigation. Here, we reviewed the latest research developments into IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.
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| 6. |
- Vimali, Jaisheela, et al.
(författare)
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Chronic Viral Infection Compromises the Quality of Circulating Mucosal-Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors
- 2024
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Ingår i: FRONTIERS IN BIOSCIENCE-LANDMARK. - : IMR PRESS. - 2768-6701. ; 29:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. Methods: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4(+) T cells including circulating Tfh cells, CD8(+) T cells, and TCR iV alpha 7.2(+) MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-alpha, IFN-gamma) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. Results: The activation marker CD69 was significantly increased in CD4(+hi) T cells, while CD8(+) MAIT cells producing IFN-gamma were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-alpha(+)CD4(+lo) T cells, CD69(+)CD8(+) T cells, CD69(+)CD4(+) MAIT cells, PD-1(+)CD4(+hi) T cells, PD-1(+)CD8(+) T cells, and Ki67(+)CD4(+) MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-alpha levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Conclusion: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.
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| 7. |
- Vimali, Jaisheela, et al.
(författare)
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Chronic viral infection compromises the quality of circulating mucosal-invariant T cells and follicular T helper cells via expression of both activating and inhibitory receptors
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we investigated the role of immune activation and compared the quality of T-cell responses in chronic HBV, HCV, and HIV infections. Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and peripheral CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. The activation marker CD69 was significantly increased in CD4+ hi T cells, while CD8+ MAIT cells expressing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+ lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+ hi T cells, PD-1+CD8+ T cells, Ki67+CD4+ MAIT cells were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. Chronic viral infection negatively impacts the quality of peripheral MAIT cells and TFH cells via expression of both activating and inhibitory receptors.
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| 8. |
- Vimali, Jaisheela, et al.
(författare)
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HIV-HPgV Co-Infected Individuals Display Functional MAIT and Follicular T Cells Irrespective of PD-1 Expression
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Human Pegivirus (HPgV) appears to alter the clinical outcome of HIV disease by modulating T-cell homeostasis, chemokine/cytokine production, as well as by reducing T-cell activation, and proliferation to limit HIV replication. Here, we evaluated if HPgV had any ‘favorable’ impact on the quantity and quality of T cells in HIV-infected individuals. T-cell subsets such as CD4lo, CD4hi, and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells, follicular helper T cells (Tfh), and follicular cytotoxic T cells (Tfc) were characterized based on the expression of markers associated with immune activation (CD69, ICOS), proliferation (ki67), cytokine production (TNF-α, IFN-γ), and exhaustion (PD-1). HIV+HPgV+ individuals had lower plasma liver transaminase SGOT and GGT (biliary) than those who were HPgV-. HIV/HPgV co-infection was significantly associated with increased absolute CD4+ T-cell counts. HIV+HPgV+ and HIV+HPgV- individuals had highly activated T-cell subsets with high expression of CD69 and ICOS on bulk CD4+ and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells and CXCR5+CD4+ T cells and CXCR5+CD8+ T cells as compared to healthy controls. Irrespective of activation markers these cells also expressed higher levels of PD-1 on CD4+ T and CD8+ T cells and their counterparts. However, exploring their functionality based on the mitogen stimulation demonstrated higher levels of cytokine production by CD4+ MAIT and CD8+ MAIT cells as compared to healthy controls. Decrease in absolute CD4+ T cell counts correlated positively with intracellular IFN-γ levels by CD4lo T cells, whereas increase of the same correlated inversely with TNF-α in the CD4lo T cells of HIV+HPgV+ individuals. Together, we found that HIV/HPgV co-infected individuals display functional CD4+ and CD8+ MAIT, Tfh and Tfc cells irrespective of PD-1 expression.
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| 9. |
- Vimali, Jaisheela, et al.
(författare)
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Human Immunodeficiency Virus-Human Pegivirus Coinfected Individuals Display Functional Mucosal-Associated Invariant T Cells and Follicular T Cells Irrespective of PD-1 Expression
- 2024
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Ingår i: Viral immunology. - : MARY ANN LIEBERT, INC. - 0882-8245 .- 1557-8976.
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Tidskriftsartikel (refereegranskat)abstract
- Human pegivirus (HPgV) appears to alter the prognosis of HIV disease by modulating T cell homeostasis, chemokine/cytokine production, and T cell activation. In this study, we evaluated if HPgV had any 'favorable' impact on the quantity and quality of T cells in HIV-infected individuals. T cell subsets such as CD4lo, CD4hi, and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells, follicular helper T (TFH) cells, and follicular cytotoxic T (TFC) cells were characterized based on the expression of markers associated with immune activation (CD69, ICOS), proliferation (ki67), cytokine production (TNF-alpha, IFN-gamma), and exhaustion (PD-1). HIV+HPgV+ individuals had lower transaminase SGOT (liver) and GGT (biliary) in the plasma than those who were HPgV-. HIV/HPgV coinfection was significantly associated with increased absolute CD4+ T cell counts. HIV+HPgV+ and HIV+HPgV- individuals had highly activated T cell subsets with high expression of CD69 and ICOS on bulk CD4+ and CD8+ T cells, CD4+ MAIT cells, CD8+ MAIT cells, and CXCR5+CD4+ T cells and CXCR5+CD8+ T cells compared with healthy controls. Irrespective of immune activation markers, these cells also displayed higher levels of PD-1 on CD4+ T and CD8+ T cells . Exploring effector functionality based on mitogen stimulation demonstrated increased cytokine production by CD4+ MAIT and CD8+ MAIT cells. Decrease in absolute CD4+ T cell counts correlated positively with intracellular IFN-gamma levels by CD4lo T cells, whereas increase of the same correlated negatively with TNF-alpha in the CD4lo T cells of HIV+HPgV+ individuals. HIV/HPgV coinfected individuals display functional CD4+ and CD8+ MAIT, TFH, and TFC cells irrespective of PD-1 expression.
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| 10. |
- Vimali, Jaisheela, et al.
(författare)
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Plasma interleukin-7 correlation with human immunodeficiency virus RNA and CD4+T cell counts, and interleukin-5 with circulating hepatitis B virus DNA may have implications in viral control
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media SA. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Chronic viral infections represent a leading cause of global morbidity and mortality. Chronic HBV, HCV, and HIV infections result in cytokine perturbations that may hold key implications in understanding the complex disease mechanisms driving virus persistence and/or resolution. Here, we determined the levels of various plasma cytokines using a commercial Bio-Plex Luminex cytokine array in chronic HBV (n = 30), HCV (n = 15), and HIV (n = 40) infections and correlated with corresponding plasma viral loads (PVLs) and liver parameters. We observed differential perturbations in cytokine profiles among the study groups. The cytokines levels positively correlated with PVL and liver transaminases. The monocyte-derived cytokines viz., MIP-1 beta, IL-8, and TNF-alpha, and Th2 cytokines like IL-4, IL-5, and IL-13 showed a better correlation with liver enzymes as compared to their corresponding PVLs. Our investigation also identified two cytokines viz., IL-5 and IL-7 that inversely correlated with HBV DNA and HIV PVLs, respectively. Regression analysis adjusted for age showed that every increase of IL-5 by one unit was associated with a reduction in HBV PVL by log(10) 0.4, whereas, every elevation by a unit of IL-7 was associated with decreased HIV PVL by log(10) 2.5. We also found that IL-7 levels correlated positively with absolute CD4+ T cell counts in HIV-infected patients. We concluded that plasma IL-5 and IL-7 may likely have a key role on viral control in HBV and HIV infections, respectively. A noteworthy increase in cytokines appears to bear protective and pathological significance, and indeed is reflective of the hosts versatile immune armory against viral persistence.
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