Translational Health Science and Technology Institute

About: Translational Health Science and Technology Institute is a government organization based out in Gurgaon, India. It is known for research contribution in the topics: Population & Virus. The organization has 467 authors who have published 861 publications receiving 15251 citations.

Lack of Interferon (IFN) Regulatory Factor 8 Associated with Restricted IFN-γ Response Augmented Japanese Encephalitis Virus Replication in the Mouse Brain.

Abstract: Interferon regulatory factor 8 (IRF8), a myeloid lineage transcription factor, emerges as an essential regulator for microglial activation. However, the precise role of IRF8 during Japanese encephalitis virus (JEV) infection in the brain remains elusive. Here, we report that JEV infection enhances IRF8 expression in the infected mouse brain. Comparative transcriptional profiling of whole-brain RNA analysis and validation by quantitative reverse transcription-PCR (qRT-PCR) reveals an impaired interferon gamma (IFN-γ) and related gene expression in Irf8 knockout (Irf8−/−)-infected mice. Further, Ifnγ knockout (Ifnγ−/−) mice exhibit a reduced level of Irf8. Both Ifnγ−/− and Irf8−/− mice exhibit significantly reduced levels of activated (CD11b+ CD45hi, CD11b+ CD45lo, Cd68, and CD86) and infiltrating immune cells (Ly6C+, CD4, and CD8) in the infected brain compared to those of wild-type (WT) mice. However, a higher level of granulocyte cell (Ly6G+) infiltration is evident in Irf8−/− mice as well as the increased concentration of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP1) levels in the brain. Interestingly, neither the Irf8−/− nor the Ifnγ−/− conferred protection against lethal JEV challenge to mice and exhibit augmentation in JEV replication in the brain. The gain of function of Irf8 by overexpressing functional IRF8 in an IRF8-deficient cell line attenuates viral replication and enhances IFN-γ production. Overall, we summarize that in the murine model of JEV encephalitis, IRF8 modulation affects JEV replication. We also show that lack of Irf8 affects immune cell abundance in circulation and the infected brain, leading to a reduction in IFN-γ level and increased viral load in the brain. IMPORTANCE Microglial cells, the resident macrophages in the brain, play a vital role in Japanese encephalitis virus (JEV) pathogenesis. The deregulated activity of microglia can be lethal for the brain. Therefore, it is crucial to understand the regulators that drive microglia phenotype changes and induce inflammation in the brain. Interferon regulatory factor 8 (IRF8) is a myeloid lineage transcription factor involved in microglial activation. However, the impact of IRF8 modulation on JEV replication remains elusive. Moreover, the pathways regulated by IRF8 to initiate and amplify pathological neuroinflammation are not well understood. Here, we demonstrated the effect of IRF8 modulation on JEV replication, microglial activation, and immune cells infiltration in the brain.

Draft Genome Sequence of an Environmental trh+ Vibrio parahaemolyticus K23 Strain Isolated from Kerala, India.

Abstract: Vibrio parahaemolyticus is the leading cause of seafood-related gastroenteritis. Here, we report the draft genome sequence of a trh+ strain, V. parahaemolyticus K23, isolated from seafood. The sequence will be useful for comparative analysis between environmental and clinical isolates of V. parahaemolyticus.

Traditional use of Cissampelos pareira L. for hormone disorder and fever provides molecular links of ESR1 modulation to viral inhibition

Abstract: In traditional systems, a single herbal formulation is often used in the treatment of diverse diseases, including some that are newly emergent and prevalent today. We provide here a multi-omics framework to probe the molecular basis of a multicomponent example herb, Cissampelos pareira L. (Cipa) used in the treatment of hormonal disorders and fever in Ayurveda. Cipa treated MCF7 cells exhibit downregulation of signatures of estrogen response. 38 constituent molecules in Cipa potentially bind ({triangleup}G 99.92. This axis was found to be upregulated in the COVID-19 patient transcriptome. The antiviral activity through ESR1 modulation was validated in the DENV-2 infection model. We further observed 98% inhibition of SARs-COV-2 replication in infected Vero cell cultures with the whole extract. A few of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. This study provides a novel framework for querying the molecular links of multicomponent Ayurveda formulations and explains their use in the treatment of disparate diseases. The novel biological targets identified here can become potential that could be applicable to more than one viral infection, such as the use of Cipa in dengue and COVID-19.