| 1. |
- Preeyaa, Sathappan U., et al.
(författare)
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Peripheral Follicular T Helper Cells and Mucosal-Associated Invariant T Cells Represent Activated Phenotypes During the Febrile Phase of Acute Dengue Virus Infection
- 2020
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Ingår i: Viral immunology. - : MARY ANN LIEBERT, INC. - 0882-8245 .- 1557-8976. ; 33:9, s. 610-615
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral follicular helper T (pTfh) cells represent specialized CD4(+)T cells that help B cells to secrete antibodies. Dengue infection appears to cause immune activation in a wide array of immune cells. Herein, we investigated the signatures of immune activation of circulating Tfh cells and mucosal-associated invariant T (MAIT) cells in adult subjects with confirmed acute clinical dengue virus (DENV) infection by multiparametric flow cytometry. The acute DENV infection induced a significant expansion and activation of pTfh cells and circulating MAIT cells during acute febrile infection. We found a higher frequency of activated PD-1(+)Tfh cells and CD38(+)pTfh cells in clinical DENV infection. We also found similar activated and expanding phenotypes of MAIT cells in the patients tested. The numbers of activated pTfh cells and circulating MAIT cells were higher in dengue patients relative to healthy controls. We concluded that pTfh cells and circulating MAIT cells represent activated phenotypes in acute DENV infection.
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| 2. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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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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Ingår i: The Lancet Regional Health - Southeast Asia. - : ELSEVIER. - 2772-3682. ; 19
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Tidskriftsartikel (refereegranskat)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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| 3. |
- 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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| 4. |
- Selvavinayagam, Sivaprakasam T., et al.
(författare)
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Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and Omicron BA.1.1.529 but not with Omicron BA.1.1 and BA.2 variants
- 2022
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Ingår i: Frontiers In Public Health. - : Frontiers Media SA. - 2296-2565. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The rapid spread of SARS-CoV-2 variants in the global population is indicative of the development of selective advantages in emerging virus strains. Here, we performed a case-control investigation of the clinical and demographic characteristics, clinical history, and virological markers to predict disease progression in hospitalized adults for COVID-19 between December 2021 and January 2022 in Chennai, India. COVID-19 diagnosis was made by a commercial TaqPath COVID-19 RT-PCR, and WGS was performed with the Ion Torrent Next Generation Sequencing System. High-quality (<5% of N) complete sequences of 73 Omicron B.1.1.529 variants were randomly selected for phylogenetic analysis. SARS-CoV-2 viral load, number of comorbidities, and severe disease presentation were independently associated with a shorter time-to-death. Strikingly, this was observed among individuals infected with Omicron BA.2 but not among those with the BA.1.1.529, BA.1.1, or the Delta B.1.617.2 variants. Phylogenetic analysis revealed severe cases predominantly clustering under the BA.2 lineage. Sequence analyses showed 30 mutation sites in BA.1.1.529 and 33 in BA.1.1. The mutations unique to BA.2 were T19I, L24S, P25del, P26del, A27S, V213G, T376A, D405N and R408S. Low SARS-CoV-2 viral load among vaccinated individuals infected with Delta B.1.617.2 and the Omicron BA.1.1.529 variant but not with Omicron BA.1.1 or BA.2 suggests that the newer strains are largely immune escape variants. The number of vaccine doses received was independently associated with increased odds of developing asymptomatic disease or recovery. We propose that the novel mutations reported herein could likely bear a significant impact on the clinical characteristics, disease progression, and epidemiological aspects of COVID-19. Surging rates of mutations and the emergence of eclectic variants of SARS-CoV-2 appear to impact disease dynamics.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- Tan, Hong-Yien, et al.
(författare)
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Mucosal-Associated Invariant T Cells: Diplomatic Front-Runners in the Fight against Hepatitis B Virus Infection
- 2021
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Ingår i: Critical Reviews in Immunology. - : BEGELL HOUSE INC. - 1040-8401 .- 2162-6472. ; 41:5, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like T cells that bridge between innate and adaptive immunity. MALT cells act like a biliary firewall protecting the epithelial lining of the liver against pathogenic intruders. MAIT1 and MAIT17 subsets respond rapidly to pathogenic presence both in the liver as well as in the peripheral circulation. In addition to chronic hepatitis B virus (HBV) infection, MAIT cells also appear to serve as potential therapeutic targets in several other chronic ailments. Evidence indicates that MAIT cells have tissue repair functions also paving way for fibrotic changes during chronic HBV infection. Observations also suggest that HBV-hepatitis delta virus (HDV) co-infection disease progression is closely associated with loss of MAIT cells. Furthermore, reduction in the number of hepatic MAIT cells in patients with cirrhotic non-alcoholic fatty liver disease and HBV-associated primary liver cancer has also been reported. Given their concrete role against HBV disease progression, and has also become evident that the tumor microenvironment can cause functional impairment of MAIT cells. Here, we reviewed the protective and the pathological role of MAIT cells in chronic HBV infection and certain other related medical conditions based on the understanding that an optimal functioning of the MAIT cell arsenal is key to a "host-friendly" immune defense against HBV disease progression.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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