https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/55 Principal Investigator- Dr. Akhil C Banerjea 2026-04-27T15:41:23Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1482 Title: Japanese Encephalitis Virus infection increases USP42 to stabilize TRIM21 and OAS1 for neuroinflammatory and anti-viral response in human microglia Authors: Banerjea, Akhil C; Mishra, Ritu; Kumawat, Kanhaiya Lal; Basu, Anirban Abstract: Japanese Encephalitis Virus (JEV), a member virus of Flaviviridae family causes Japanese encephalitis (JE). JE is a mosquito-borne disease, spread mainly by Culex spp. During JE, dysregulated inflammatory responses play a central role in neuronal death and damage leading to Neuroinflammation. In this study, we show that JEV infection in human microglial cells (CHME3) reduces the cellular miR-590-3p levels. miR-590-3p could directly target the expression levels of USP42 (Ubiquitin Specific Peptidase 42) resulting in increased cellular levels of USP42 upon JEV infection. Our results suggest that USP42 stabilizes cellular TRIM21 via deubiquitinating them. We also established through various in vitro and in vivo experiments that increased USP42 can maintain a higher cellular level of both TRIM21 as well as OAS1. This study also suggests that TRIM21, independently of its RING domain, can increase USP42 level in a positive feedback loop and induces the cellular OAS1 levels in human microglial cells. 2022-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1409 Title: n-Vitro Subtype-Specific Modulation of HIV-1 Trans-Activator of Transcription (Tat) on RNAi Silencing Suppressor Activity and Cell Death Authors: Banerjea, Akhil C; Ronsard, Larance; Yousif, Ashraf S; Ramesh, Janani; Sumi, N; Gorman, Matthew; Ramachandran, Vishnampettai G Abstract: Human immunodeficiency virus (HIV) is a global health concern affecting millions of individuals with a wide variety of currently circulating subtypes affecting various regions of the globe. HIV relies on multiple regulatory proteins to modify the host cell to promote replication in infected T cells, and these regulatory proteins can have subtle phenotypic differences between subtypes. One of these proteins, HIV-1 Trans-Activator of Transcription (Tat), is capable of RNA interference (RNAi) Silencing Suppressor (RSS) activity and induction of cell death in T cells. However, the subtype-specific RSS activity and induction of cell death have not been explored. We investigated the ability of Tat subtypes and variants to induce RSS activity and cell death. TatB, from HIV-1 subtype B, was found to be a potent RSS activator by 40% whereas TatC, from HIV-1 subtype C, showed 15% RSS activity while subtype TatC variants exhibited varying levels. A high level of cell death (50-53%) was induced by subtype TatB when compared to subtype TatC (25-28%) and varying levels were observed with subtype TatC variants. These differential activities could be due to variations in the functional domains of Tat. These observations further our understanding of subtype-specific augmentation of Tat in HIV-1 replication and pathogenesis. 2019-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1408 Title: s8ORF2 protein of infectious salmon anaemia virus is a RNA-silencing suppressor and interacts with Salmon salar Mov10 (SsMov10) of the host RNAi machinery Authors: Banerjea, Akhil C; Mukherjee, Sunil K; Zaidi, Rana; Rimstad, Espen; Lal, Sunil K; Thukral, Vandana; Varshney, Bhavna; Ramly, Rimatulhana B; Ponia, Sanket S; Mishra, Sumona Karjee; Olsen, Christel M Abstract: The infectious salmon anaemia virus (ISAV) is a piscine virus, a member of Orthomyxoviridae family. It encodes at least 10 proteins from eight negative-strand RNA segments. Since ISAV belongs to the same virus family as Influenza A virus, with similarities in protein functions, they may hence be characterised by analogy. Like NS1 protein of Influenza A virus, s8ORF2 of ISAV is implicated in interferon antagonism and RNA-binding functions. In this study, we investigated the role of s8ORF2 in RNAi suppression in a well-established Agrobacterium transient suppression assay in stably silenced transgenic Nicotiana xanthi. In addition, s8ORF2 was identified as a novel interactor with SsMov10, a key molecule responsible for RISC assembly and maturation in the RNAi pathway. This study thus sheds light on a novel route undertaken by viral proteins in promoting viral growth, using the host RNAi machinery. 2018-01-01T00:00:00Z https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1407 Title: Hyperactivation of mammalian target of rapamycin complex 1 by HIV-1 is necessary for virion production and latent viral reactivation Authors: Banerjea, Akhil C Abstract: Generation of new HIV-1 virions requires the constant supply of proteins, nucleotides, and energy; however, it is not known which cellular pathways are perturbed and what molecular mechanisms are employed. We hypothesized that HIV-1 may regulate pathways that control synthesis of biomolecules in the cell. In this study, we provide evidence that HIV-1 hyperactivates mammalian target of rapamycin complex 1 (mTORC1), the central regulator of biosynthesis. Mechanistically, we identify the viral regulatory gene tat (transactivator) as being responsible for increasing mTORC1 activity in a PI3K-dependent manner. Furthermore, we show that hyperactivation of mTORC1 leads to activation of the enzyme, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase, and repression of initiation factor 4E-binding protein 1 activity. These are regulators of nucleotide biogenesis and protein translation, respectively. Moreover, we are able to replicate these results in HIV-1 latent cell line models. Finally, we show that inhibition of mTORC1 or PI3K inhibits viral replication and viral reactivation as a result of a decrease in biosynthesis. Overall, our study identifies a new avenue in HIV-1 biology that can lead to development of novel therapeutic targets.-Kumar, B., Arora, S., Ahmed, S., Banerjea, A. C. Hyperactivation of mammalian target of rapamycin complex 1 by HIV-1 is necessary for virion production and latent viral reactivation. 2017-01-01T00:00:00Z