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.

A Pregnancy Cohort to Study Multidimensional Correlates of Preterm Birth in India: Study Design, Implementation, and Baseline Characteristics of the Participants.

Abstract: Globally, preterm birth is a major public health problem. In India, 3.6 million of the 27 million infants born annually are preterm. Risk stratification of women based on multidimensional risk factors assessed during pregnancy is critical for prevention of preterm birth. A cohort study of pregnant women was initiated in May 2015 at the civil hospital in Gurugram, Haryana, India. Women are enrolled within 20 weeks of gestation and are followed until delivery and once postpartum. The objectives are to identify clinical, epidemiologic, genomic, epigenomic, proteomic, and microbial correlates; discover molecular-risk markers by using an integrative -omics approach; and generate a risk-prediction algorithm for preterm birth. We describe here the longitudinal study design, methodology of data collection, and the repositories of data, biospecimens, and ultrasound images being created. A total of 4,326 pregnant women, with documented evidence of recruitment before 20 weeks of gestation, have been enrolled through March 2018. We report baseline characteristics and outcomes of the first 2,000 enrolled participants. A high frequency of preterm births (14.9% among 1,662 live births) is noteworthy. The cohort database and the repositories will become global resources to answer critical questions on preterm birth and other birth outcomes.

Host-Virus Protein Interaction Network Reveals the Involvement of Multiple Host Processes in the Life Cycle of Hepatitis E Virus.

Abstract: Comprehensive knowledge of host-pathogen interactions is central to understand the life cycle of a pathogen and devise specific therapeutic strategies. Protein-protein interactions (PPIs) are key mediators of host-pathogen interactions. Hepatitis E virus (HEV) is a major cause of viral hepatitis in humans. Recent reports also demonstrate its extrahepatic manifestations in the brain. Toward understanding the molecular details of HEV life cycle, we screened human liver and fetal brain cDNA libraries to identify the host interaction partners of proteins encoded by genotype 1 HEV and constructed the virus-host PPI network. Analysis of the network indicated a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed the presence of multiple host translation regulatory factors in the viral translation/replication complex. Depletion of host translation factors such as eIF4A2, eIF3A, and RACK1 significantly reduced the viral replication, whereas eIF2AK4 depletion had no effect. These findings highlight the ingenuity of the pathogen in manipulating the host machinery to its own benefit, a clear understanding of which is essential for the identification of strategic targets and development of specific antivirals against HEV. IMPORTANCE Hepatitis E virus (HEV) is a pathogen that is transmitted by the fecal-oral route. Owing to the lack of an efficient laboratory model, the life cycle of the virus is poorly understood. During the course of infection, interactions between the viral and host proteins play essential roles, a clear understanding of which is essential to decode the life cycle of the virus. In this study, we identified the direct host interaction partners of all HEV proteins and generated a PPI network. Our functional analysis of the HEV-human PPI network reveals a role of HEV proteins in modulating multiple host biological processes such as stress and immune responses, the ubiquitin-proteasome system, energy and iron metabolism, and protein translation. Further investigations revealed an essential role of several host factors in HEV replication. Collectively, the results from our study provide a vast resource of PPI data from HEV and its human host and identify the molecular components of the viral translation/replication machinery.

N-Desmethylclozapine, Fluoxetine, and Salmeterol Inhibit Postentry Stages of the Dengue Virus Life Cycle

Abstract: Around 10,000 people die each year due to severe dengue disease, and two-thirds of the world population lives in a region where dengue disease is endemic. There has been remarkable progress in dengue virus vaccine development; however, there are no licensed antivirals for dengue disease, and none appear to be in clinical trials. We took the approach of repositioning approved drugs for anti-dengue virus activity by screening a library of pharmacologically active compounds. We identified N-desmethylclozapine, fluoxetine hydrochloride, and salmeterol xinafoate as dengue virus inhibitors based on reductions in the numbers of infected cells and viral titers. Dengue virus RNA levels were diminished in inhibitor-treated cells, and this effect was specific to dengue virus, as other flaviviruses, such as Japanese encephalitis virus and West Nile virus, or other RNA viruses, such as respiratory syncytial virus and rotavirus, were not affected by these inhibitors. All three inhibitors specifically inhibited dengue virus replication with 50% inhibitory concentrations (IC50s) in the high-nanomolar range. Estimation of negative-strand RNA intermediates and time-of-addition experiments indicated that inhibition was occurring at a postentry stage, most probably at the initiation of viral RNA replication. Finally, we show that inhibition is most likely due to the modulation of the endolysosomal pathway and induction of autophagy.