Vijaya Satchidanandam - Academia.edu (original) (raw)

Papers by Vijaya Satchidanandam

Fems Microbiology Letters, 2003

Elsevier eBooks, 1990

A review, with 63 refs. Vanadate stimulates oxidn. of NADH and NADPH nonenzymically and the rate ... more A review, with 63 refs. Vanadate stimulates oxidn. of NADH and NADPH nonenzymically and the rate of the reaction is enhanced by enzymes in plasma and microsomal membranes with NADH, and by xanthine oxidase with both NADH and NADPH. This H2O2H_2O_2H2O2-generating reaction, with a stoichiometry of NADH−O2−H2O_2NADH-O_2-H_2O_2NADH−O_2−H2O2 of 1:1:1, is unusual in its inhibition by SOD which made its acceptance initially difficult. The first equiv. of NADH being used for a SOD-insensitive redn. of vanadate to a blue compd. in microsomes, caution is suggested in interpretation of SOD effects. The activity is high with polymeric vanadate. The low activity with metavanadate increases on acidification/polymn., chem. redn. to vanadyl and presence of H2O2H_2O_2H2O2, or converting into oxo-peroxo vanadate by treatment with H2O2H_2O_2H_2O_2. A common structural feature of O:V-O-V:O with IR band of 985 cm−1cm^{-1}cm−1 is noticed in all active vanadate forms. Mechanisms not involving superoxide need to be considered now in view of doubts on its formation in this reaction. Vanadate participates in several redox activities such as NADH oxidn., nitrogenase, lipid peroxidn. and bromoperoxidase, with H-abstraction being the core reaction.

Frontiers in Immunology (Web), 2017

Journal of the Indian Institute of Science, Jan 7, 2013

The Centre for Genetic Engineering was created in 1988 to foster basic research using recombinant... more The Centre for Genetic Engineering was created in 1988 to foster basic research using recombinant DNA techniques. Several research programmes are operative in the areas of transcription,translation, molecular basis of viral and bacterial pathogenesis and tumongenesis. In addition, molecular and immunological aspects of tuberculosis are being actively pursued. This profile describes in a nutshell the research programme of the Centre.

Molecular and Cellular Biochemistry, 1992

The oxidation of NADH and accompanying reduction of oxygen to H2O2 stimulated by polyvanadate was... more The oxidation of NADH and accompanying reduction of oxygen to H2O2 stimulated by polyvanadate was markedly inhibited by SOD and cytochrome c. The presence of decavanadate, the polymeric form, is necessary for obtaining the microsomal enzyme-catalyzed activity. The accompanying activity of reduction of cytochrome c was found to be SOD-insensitive and therefore does not represent superoxide formation. The reduction of cytochrome c by vanadyl sulfate was also SOD-insensitive. In the presence of H2O2, all the forms of vanadate were able to oxidize reduced cytochrome c, which was sensitive to mannitol, tris and also catalase, indicating H2O2-dependent generation of hydroxyl radicals. Using ESR and spin trapping technique only hydroxyl radicals, but not superoxide anion radicals, were detected during polyvanadate-dependent NADH oxidation.

We show that Rv3881c, a secreted protein of M. tuberculosis (MTB), elicits T cell responses from ... more We show that Rv3881c, a secreted protein of M. tuberculosis (MTB), elicits T cell responses from healthy PPD-positive individuals and TB patients. Synthetic peptides spanning the complete length of Rv3881c induced secretion of significantly greater levels of TNF-α and IL-10 from peripheral blood mononuclear cells of TB patients compared to latently infect healthy volunteers. Polychromatic flow cytometry detected poly-functional CD4+ and CD8+ T cells secreting different combinations of IFN-γ, TNF-α, IL-2 and MIP-1β in response to Rv3881c. Levels of CD4+ T cells secreting either IFN-γ or TNF-α were significantly higher in TB patients while levels of CD8+ T cells secreting both IFN-γ and IL-2 were significantly greater in healthy PPD-positive volunteers.

JEV exposed human volunteers comprising healthy contacts and recovered JEV patients were recruite... more JEV exposed human volunteers comprising healthy contacts and recovered JEV patients were recruited for this study. Individuals who received the live attenuated JE vaccine SA14-14-2 were also included. Blood drawn was stimulated with capsid, envelope and NS3 proteins of JEV, PS cells uninfected and infected with JEV along with cells alone controls. The FACS antibody panel consisting of anti-CD3-APC-H7 (clone SK7), anti-CD8-PerCP (clone SK1), anti-IFN--PECy7 (clone B27), anti-IL-2-FITC (MQ1-17H12), anti-TNFα-APC (6401-1111) and anti-MIP-1β-PE (11A3), from BD Pharmingen, San Diego, CA.

Critical Reviews in Immunology, 2021

Flaviviruses are zoonotic encephalitogenic pathogens of humans and animals that are transmitted b... more Flaviviruses are zoonotic encephalitogenic pathogens of humans and animals that are transmitted by arthropod vectors. Effective vaccines against all but the yellow fever virus and the Japanese encephalitis virus among flaviviruses have eluded the persistent efforts of researchers. CD8+ cytotoxic T lymphocytes play a critical role in control of intracellular pathogens and hence are expected to contribute significantly to protection against flavivirus disease, while their ability to destroy infected neurons is bound to result in damage to the central nervous system (CNS). This review summarizes scientific investigations that revealed the wide spectrum of effects of CD8+ T cells both in virus control within the CNS as well as the range of pathologies exhibited by CD8+ T cells during infections by the individual members of this genus. The unique cross-reactive nature of CD8+ T cells specific to numerous flaviviruses and their implication for vaccine design are discussed.

The COVID-19 pandemic has highlighted the need for novel antivirals for pandemic management and p... more The COVID-19 pandemic has highlighted the need for novel antivirals for pandemic management and preparedness. Targeting host processes that are co-opted by viruses is an attractive strategy for developing antivirals with a high resistance barrier. Picolinic acid (PA) is a byproduct of tryptophan metabolism, endogenously produced in humans and other mammals. Here we report broad-spectrum antiviral effects of PA against enveloped viruses, including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), Influenza A virus (IAV), Flaviviruses, Herpes Simplex Virus, and Human Parainfluenza Virus. We further demonstrate using animal models that PA is effective against SARS-CoV-2 and IAV, especially as an oral prophylactic. The mode of action studies revealed that PA inhibits viral entry of enveloped viruses, primarily by interfering with viral-cellular membrane fusion, inhibiting virus-mediated syncytia formation, and dysregulating cellular endocytosis. Overall, our data establish P...

Fluorescence minus four controls for flow cytometry experiments of innate immune cytokine product... more Fluorescence minus four controls for flow cytometry experiments of innate immune cytokine production in response to dengue virus. Pseudo color flow cytometry plots for a representative patient comparing the fluorescence minus four (FMF; top row) control with completely stained sample (bottom) for secretion of (A) TNF-α, (B) IP-10, (C) IL-10, (D) IL-6 and (E) IFN-γ from the indicated cell subsets. Abbreviations: CM – CD14+CD16- classical monocytes; IM – CD14+CD16+ intermediate monocytes; NCM – CD14-CD16+ non-classical monocytes; G – Granulocytes; NKT – CD56+CD3+ natural killer T cells; NK++ - CD56+CD16+ natural killer cells; NK+- - CD56+CD16- natural killer cells; B – CD19+ cells.

An approach for studying the mediators of pathogenesis in Mycobacterium tuberculosis

Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 56001 2, Indi... more Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 56001 2, India Seven novel antigens of Mycobacterium tubersulosis, which had previously been identified based on reactivity to sera from patients with tuberculosis, were characterized. Nucleotide sequence analysis of the genes encoding these seven antigens identified one of them as the FtsH and a second as the aminoimidazole ribotide synthase of M. tuberculosis. Antisera raised to the recombinant forms of each of these seven antigens were used to study the distribution of these proteins within mycobacterial species as well as to determine their subcellular localization and hydrophobicity. Four of the seven antigens were conserved only among pathogenic strains of mycobacteria. Of the seven proteins studied, FtsH and a second protein of unknown identity were localized in membranes. Two were cytosolic, while two others, which had a high proline content, were tightly associated with the cell wall. One pr...

BCG shows increased survival in MTSA-DCs. Either fully differentiated MTSA-DCs (MTSA) or GM-CSF D... more BCG shows increased survival in MTSA-DCs. Either fully differentiated MTSA-DCs (MTSA) or GM-CSF DCs (GM-CSF) were infected with M. bovis BCG at 1 MOI for 5 h. Following elimination of extracellular bacteria by gentamicin treatment, cells were cultured for 72 h. At the end of the incubation period, cells were lysed, and cell lysate was serially diluted and plated for CFU monitoring on 7H10 agar plates. In some groups, GM-CSF DCs were treated with either 50 mM NAc or 10 M DPI or 100 ng/ml PMA, or 1 M ionomycin (iono), whereas MTSA-DCs were treated with either 50 M H 2 O 2 or 0.1 M calphostin C (cal C) or 1 M ionomycin (iono) for 1 h before infection. Data from one of three independent experiments are shown.

The Journal of …, 2006

We investigated the role of reactive oxygen species (ROS) in dendritic cell (DC) differentiation ... more We investigated the role of reactive oxygen species (ROS) in dendritic cell (DC) differentiation by 10-kDa Mycobacterium tuberculosis secretory Ag (MTSA) and survival of mycobacteria therein. Compared with GM-CSF, MTSA induced lower ROS production during DC ...

Clinical Infectious Diseases

Background Early and accurate diagnosis followed by timely treatment are the key prerequisites to... more Background Early and accurate diagnosis followed by timely treatment are the key prerequisites to fight tuberculosis (TB) and reduce its global burden. Despite scientific advances, the rapid and correct diagnosis of both pulmonary and extrapulmonary tuberculosis remains a challenge because of traditional reliance on detection of the elusive bacilli. Mycobacterium tuberculosis (Mtb)-specific host immune activation and cytokine production have shown significant promise as alternative means of detecting and distinguishing active disease from latent infection. We queried the diagnostic ability of phenotypic markers on Mtb-specific cytokine-producing immune cell subsets for identifying active TB. Methods Subjects belonging to the following groups were recruited: pulmonary and extrapulmonary TB, latent TB, cured TB, sick controls, and healthy controls. Polychromatic flow cytometry was used to identify host immune biomarkers in an exploratory cohort comprising 56 subjects using peripheral ...

Current Treatment Options in Infectious Diseases

Purpose of review As an eminently vaccine-preventable disease, encephalitis caused by Japanese en... more Purpose of review As an eminently vaccine-preventable disease, encephalitis caused by Japanese encephalitis virus (JEV) has attracted an unusually high degree of attention from those seeking to develop viral vaccines. Since the 1950s, all types of JEV vaccines including inactivated, recombinant and live attenuated ones have been licensed. As an example of an extremely successful endeavour, the time is ripe for reviewing the development of JEV vaccines and probing the reasons behind their uniform success. Recent findings Vaccines against JEV have come a long way since the first licensing in the mid-1950s of the mouse brain-grown-inactivated virus preparations, to the present day live-attenuated virus vaccines. A survey of the various inactivated and live vaccines developed against JEV provides a striking insight into the impressive safety and efficacy of all the vaccines available to prevent encephalitis from JEV. This review juxtaposes studies to understand naturally acquired immunity against JEV that have mostly been published post-2000, compares these with those elicited by vaccines and highlights the paucity of data on cell-mediated immune responses elicited by JEV vaccines. Summary This article not only seeks to make available the immense salient literature on this endeavour in one collection, but also queries the basis for the remarkable success of JEV vaccines, not least of which may be the ease of protecting against encephalitis caused by JEV. To conclude, the true test of the ingenuity of those dedicated to the pursuit of viral vaccines would be success against viral diseases such as HIV-AIDS and dengue that pose a far greater challenge to scientists.

Biomarkers of progression to severe dengue are urgently required for effective patient management... more Biomarkers of progression to severe dengue are urgently required for effective patient management. Innate immune cells have been implicated in the enhancement of infection and “cytokine storm” associated with dengue severity. Using intracellular cytokine staining and flow cytometry, we observed significantly higher proportions of innate immune cells secreting inflammatory cytokines dominated by IFN-γ and TNF-α at admission associated with good prognosis. Secondary dengue predisposed to severe outcomes. In patients with severe dengue and those with liver impairment, early activation as well as efficient down-regulation of innate responses were compromised. IFN-γ+CD56+CD3+NKT cells and IL-6+granulocytes served as novel biomarkers of progression to severity (composite AUC=0.85-0.9). Strong correlations among multiple cytokine-secreting innate cell subsets pointed to coordinated activation of the entire innate immune system by DENV.One Sentence SummaryActivation and efficient attenuatio...

ABSTRACTThe live attenuated Japanese encephalitis virus vaccine SA14-14-2 demonstrated ≥ 95 % eff... more ABSTRACTThe live attenuated Japanese encephalitis virus vaccine SA14-14-2 demonstrated ≥ 95 % efficacy and is today the vaccine of choice against JEV globally. Relative to its parent strain SA14, SA14-14-2 carries 46 nucleotide and 24 amino acid alterations, with 8 of the latter located within the envelope glycoprotein. The vaccine strain also fails to synthesize the nonstructural protein NS1’ owing to a silent mutation that abrogates a-1-frameshifting event close to the 5’ end of the NS2A coding sequence. Previous studies employing reverse genetics and mouse models implicated both absence of NS1’ and mutated E, in attenuation of SA14-14-2. We demonstrate progressive reduction in ER stress sensor PERK levels and increased expression of CEBP-homologous protein (CHOP), accompanied by dephosphorylation of eIF2α, inhibition of autophagy maturation and necroptosis following infection of cultured cells with wild-type JEV strain P20778. Autonomous expression of NS1’ caused constitutive up-...

SSRN Electronic Journal

ABSTRACTRATIONALEEarly and accurate diagnosis followed by timely treatment are the key prerequisi... more ABSTRACTRATIONALEEarly and accurate diagnosis followed by timely treatment are the key prerequisites to fight tuberculosis (TB) and reduce its global burden. Despite scientific advances, the rapid and correct diagnosis of both pulmonary and extrapulmonary tuberculosis remains a challenge due to traditional reliance on detection of the elusive bacilli. Mycobacterium tuberculosis (Mtb)-specific host immune activation and cytokine production has shown significant promise as an alternative means of detecting and distinguishing active disease from latent infection.OBJECTIVEPhenotypic characteristics of Mtb-specific cytokine-producing immune cell subsets were investigated and queried for their diagnostic ability in identifying active tuberculosis.METHODSSubjects belonging to the following groups were recruited – pulmonary, extrapulmonary, latent TB, cured TB, sick controls and healthy controls. Polychromatic flow cytometry was used to identify host immune biomarkers in an exploratory cohort comprising 56 subjects using peripheral blood mononuclear cells. Clinical performance of the identified biomarker was evaluated using whole blood in a blinded validation cohort comprising 165 individuals.FINDINGSFrequencies of Mtb-specific CD4+ T cells of the phenotype CD38+CD27− clearly distinguished patients with active tuberculosis from individuals without the disease. CD38+CD27−CD4+ T cells secreting TNF-α upon stimulation with ESAT6/CFP10 peptides had the best diagnostic accuracy at a cut-off of 9.91% [exploratory: 96.67% specificity, 88.46% sensitivity; validation: 96.15% specificity, 90.16% sensitivity]. Additionally, this subset differentiated treatment-naive TB patients from individuals cured of TB following completion of anti-tuberculosis therapy.INTERPRETATIONMtb-specific CD38+CD27−TNF-α+CD4+ T cell subset is a robust biomarker for TB diagnosis and can determine cure.IMPACT OF THIS RESEARCHWe identified and validated CD38+CD27−TNF-α+ as a robust biomarker with diagnostic accuracies >90% in both PBMCs and whole blood that can be translated into a reliable and cost-effective in vitro diagnostic test with ease. By not removing samples with insignificant immune response and instead classifying them as negative, our study represents a truly realistic assessment of the diagnostic accuracy of the identified biomarker in a clinical setting.