Arup Banerjee
@rcb.res.in
Associate Professor
Regional Centre for Biotechnology
RESEARCH, TEACHING, or OTHER INTERESTS
Biochemistry, Genetics and Molecular Biology, Immunology and Microbiology, Molecular Biology, Virology
Scopus Publications
Scopus Publications
Surender Rawat, Shubham Kumar, Shweta Duggal, and Arup Banerjee
Oxford University Press (OUP)
Abstract Neutrophils are the most abundant granuloytes, are phenotypically heterogeneous, and exert detrimental or protective roles during antiviral response. Dengue virus has been reported to activate neutrophils. However, the effect of the dengue virus on the neutrophil phenotypes, survival, and release of inflammatory secretome is yet to be understood. Herein, we investigated the effect of dengue virus serotype 2 (DV-2) on effector functions of naïve neutrophils and studied the impact of its secretome on different immune cells. We found that DV-2 activates purified human neutrophils and causes a significant shift toward the CD16bright/CD62Ldim subtype in a multiplicity of infection and time-dependent manner. These phenotypically altered neutrophils show delayed apoptosis through nuclear factor κB and PI3K pathways and have decreased phagocytic capacity. Treatment of neutrophils with myeloperoxidase and PAD4 inhibitor before DV-2 incubation significantly reduced DV-2–induced double-stranded DNA release, suggesting that myeloperoxidase and PAD4 were involved at early stages for the neutrophil activation and double-stranded DNA release. We also report that DV-2–stimulated neutrophil secretome had a significant effect on viral infection, platelet activation, and naïve neutrophil survival via binding of tumor necrosis factor α to tumor necrosis factor receptor 1/2 receptors. Furthermore, incubation of endothelial cells with the DV-2–stimulated neutrophil secretome potentially inhibits proliferation and wound healing capacity and induces endothelial cell death, which can contribute to endothelial barrier dysfunction. In conclusion, the neutrophil–DV-2 interaction modulates the phenotype of neutrophils and the release of prosurvival and antiviral secretome that may act as a double-edged sword during dengue pathogenesis.
Surendra K Prajapat, Laxmi Mishra, Sakshi Khera, Shadrack D Owusu, Kriti Ahuja, Puja Sharma, Eira Choudhary, Simran Chhabra, Niraj Kumar, Rajan Singh,et al.
Springer Science and Business Media LLC
AbstractJapanese encephalitis virus (JEV) pathogenesis is driven by a combination of neuronal death and neuroinflammation. We tested 42 FDA-approved drugs that were shown to induce autophagy for antiviral effects. Four drugs were tested in the JE mouse model based on in vitro protective effects on neuronal cell death, inhibition of viral replication, and anti-inflammatory effects. The antipsychotic phenothiazines Methotrimeprazine (MTP) & Trifluoperazine showed a significant survival benefit with reduced virus titers in the brain, prevention of BBB breach, and inhibition of neuroinflammation. Both drugs were potent mTOR-independent autophagy flux inducers. MTP inhibited SERCA channel functioning, and induced an adaptive ER stress response in diverse cell types. Pharmacological rescue of ER stress blocked autophagy and antiviral effect. MTP did not alter translation of viral RNA, but exerted autophagy-dependent antiviral effect by inhibiting JEV replication complexes. Drug-induced autophagy resulted in reduced NLRP3 protein levels, and attenuation of inflammatory cytokine/chemokine release from infected microglial cells. Our study suggests that MTP exerts a combined antiviral and anti-inflammatory effect in JEV infection, and has therapeutic potential for JE treatment.
Shweta Duggal, Surender Rawat, Gazala Siddqui, Preeti Vishwakarma, Sweety Samal, Arup Banerjee, and Sudhanshu Vrati
Oxford University Press (OUP)
Abstract While neutrophil activation during dengue virus infection is known, the effect of dengue virus infection on neutrophil biogenesis has not been studied. We demonstrate that dengue virus serotype 2 induces the differentiation of mice progenitor cells ex vivo toward the CD11b+Ly6C+Ly6G+ granulocyte population. We further observed an expansion of CD11b+Ly6CintLy6Glow myeloid cells in the bone marrow of dengue virus serotype 2–infected AG129 mice with low CXCR2 expression, implying an immature population. Additionally, dengue virus serotype 2 alone could induce the differentiation of promyelocyte cell line HL-60 into neutrophil-like cells, as evidenced by increased expression of CD10, CD66b, CD16, CD11b, and CD62L, corroborating the preferential shift toward neutrophil differentiation by dengue virus serotype 2 in the mouse model of dengue infection. The functional analysis showed that dengue virus serotype 2–induced neutrophil-like cells exhibited reduced phagocytic activity and enhanced NETosis, as evidenced by the increased production of myeloperoxidase, citrullinated histones, extracellular DNA, and superoxide. These neutrophil-like cells lose their ability to proliferate irreversibly and undergo arrest in the G0 to G1 phase of the cell cycle. Further studies show that myeloperoxidase-mediated signaling operating through the reactive oxygen species axis may be involved in dengue virus serotype 2–induced proliferation and differentiation of bone marrow cells as ABAH, a myeloperoxidase inhibitor, limits cell proliferation in vitro and ex vivo, affects the cell cycle, and reduces reactive oxygen species production. Additionally, myeloperoxidase inhibitor reduced NETosis and vascular leakage in dengue virus serotype 2–infected AG129 mice. Our study thus provides evidence that dengue virus serotype 2 can accelerate the differentiation of bone marrow progenitor cells into neutrophils through myeloperoxidase and modulate their functions.
Sharda Kumari, Bhaswati Bandyopadhyay, Anamika Singh, Suruchi Aggarwal, Amit Kumar Yadav, Naval Kishore Vikram, Prasenjit Guchhait, and Arup Banerjee
American Society for Microbiology
ABSTRACT Extracellular vesicles (EVs) are small membrane vesicles secreted into biological fluids, which play crucial roles in influencing the cellular function in different pathological processes. However, there is less clarity on how plasma EVs influence proliferation activation and functions of immune cells during dengue virus (DV) infection. In this study, we aimed to characterize circulating EVs from different categories of dengue patients and examined the consequence of naïve CD4+ T cells to EVs isolated from the plasma of mild or severe dengue patients. We observed that severe dengue infection was associated with an increased release of CD41a+ platelet extracellular vesicles compared with that from patients with mild disease or healthy donors. These EVs carried an increased level of pro- and anti-inflammatory cytokines along with immunoregulatory proteins on the surface that caused CD4+ T cell suppression. Treatment of purified naïve CD4+ T cells with EVs derived from severe dengue plasma drove CD4+ proliferation toward specific subtypes and modulated surface receptor CXCR3 and CCR6 expression. Subsequent studies indicated a notable rise in programmed cell death ligand 1 (PD-L1) expression within CD41a+ severe DV (SDV) EVs. Additionally, CD4+ T cells showed an elevated increase in programmed cell death 1 (PD-1) after incubating with SDV-EVs. We also demonstrated that blocking PD-L1 on SDV-EVs or PD-1 on late-activating CD4 + T cells partially reversed the SDV-EV-induced suppression of CD4+ T cell proliferation. Overall, our study highlights the immunosuppressive property of EVs derived from plasma of severe dengue patients, which might contribute to immune pathogenesis by shaping the immune response. IMPORTANCE Severe dengue manifestations caused by the dengue virus are a global health problem. Studies suggest that severe dengue disease depends on uncontrolled immune cell activation, and excessive inflammation adds to the pathogenesis of severe dengue disease. Therefore, it is important to understand the process that triggers the uncontrolled activation of the immune cells. The change in immune response in mild to severe dengue may be due to direct virus-to-cell interaction or it could be a contact-independent process through the extracellular vesicles (EVs) released from infected cells. The importance of circulating EVs in the context of dengue virus infection and pathogenesis remains unexplored. Therefore, understanding the possible biological function of circulating EVs may help to delineate the role of EVs in the progression of disease. Our present study highlights that EVs from plasma of severe dengue patients can have immunosuppressive properties on CD4+ T cells which may contribute to T cell suppression and may contribute to dengue disease progression.
Jaya Saini, Umesh Thapa, Bhaswati Bandyopadhyay, Sudhanshu Vrati, and Arup Banerjee
Microbiology Society
The lncRNA NEAT1 plays a vital role in mitochondrial function and antiviral response. We have previously identified NEAT1 as dysregulated lncRNAs and found an inverse correlation with interferon alpha-inducible protein 27 (IFI27) expression associated with developing dengue severity. However, the role of NEAT1 in dengue virus (DV) infection remains elusive. Here, we undertook a study to evaluate the functional consequences of NEAT1 and IFI27 modulation on antiviral response and viral replication in dengue infection. We observed that the knockdown of NEAT1 augmented IFI27 expression and antiviral response via the RIG-I pathway. Increased antiviral response leads to a decrease in dengue viral replication. Further study suggested that the knockdown of IFI27 augmented expression of the activating transcription factor 3 (ATF3), a negative regulator of antiviral response, and increased dengue virus replication suggesting an important role played by IFI27 in mediating antiviral response. RNA sequencing study confirmed several mitochondrial genes significantly altered upon knockdown of NEAT1 in DV-infected cells. We further verified the effect of NEAT1 knockdown on mitochondrial functions. We observed a reduced level of phospho-DRP1(S616) expression along with elongated mitochondria in DV2-infected cells. Further, NEAT1 knockdown or ectopic expression of IFI27 increased mitochondrial ROS production and cell death via activation of caspase 3. Our study points to the crucial role of NEAT1 and IFI27 in mediating antiviral response and mitochondrial dysfunction in dengue infection.
Anjali Barnwal, Brohmomoy Basu, Aarti Tripathi, Naina Soni, Debasish Mishra, Arup Banerjee, Rajesh Kumar, Sudhanshu Vrati, and Jayanta Bhattacharyya
American Chemical Society (ACS)
The onset and spread of the SARS-CoV-2 virus have created an unprecedented universal crisis. Although vaccines have been developed against the parental SARS-CoV-2, outbreaks of the disease still occur through the appearance of different variants, suggesting a continuous need for improved and effective therapeutic strategies. Therefore, we developed a novel nanovesicle presenting Spike protein on the surface of the dendritic cell-derived extracellular vesicles (DEVs) for use as a potential vaccine platform against SARS-CoV-2. DEVs express peptide/MHC-I (pMHC-I) complexes, CCR-7, on their surface. The immunogenicity and efficacy of the Spike-activated DEVs were tested in mice and compared with free Spike protein. A 1/10 Spike equivalent dose of DEVs showed a superior potency in inducing anti-Spike IgG titers in blood of mice when compared to dendritic cells or free Spike protein treatment. Moreover, DEV-induced sera effectively reduced viral infection by 55–60% within 15 days of booster dose administration. Furthermore, a 1/10 Spike equivalent dose of DEV-treated mice was found to be equally effective in inducing CD19+CD38+ T-cells in the spleen and lymph node; CD8 cells in the bone marrow, spleen, and lymph node; and CD4+CD25+ T-cells in the spleen and lymph node after 90 days of treatment. Thus, our results support the immunogenic nature of DEVs, demonstrating that a low dose of DEVs induces antibodies to inhibit SARS-CoV-2 infection in vitro, therefore warranting further investigations.
Naina Soni, Aarti Tripathi, Sriparna Mukherjee, Suchi Gupta, Sujata Mohanty, Anirban Basu, and Arup Banerjee
Wiley
Mesenchymal stem cells (MSCs) have regenerative capacity and have reported a beneficial effect on the Japanese encephalitis virus (JEV) in an encephalitis model. However, the MSCs do not cross the blood–brain barrier and have other disadvantages limiting their therapeutic utility scope. Recently, there has been a shift in concept from a cell‐based to a cell‐free approach using MSCs‐derived extracellular vesicles (MSC‐EVs). The MSC‐EVs retain regenerative and immunomodulatory capacity as their parental cells. However, the role of MSC‐EVs in limiting JEV pathology remains elusive. In this study, we have used Bone marrow (BM)‐derived EV (BM‐EVs) and assessed their effect on JEV replication and pathogenesis in primary neuronal stem cells and a murine model. The in vitro and in vivo studies suggested that BM‐derived EVs delay JEV‐induced symptoms and death in mice, improve the length of survival, accelerate neurogenesis in primary neuronal stem cells, reduce JEV‐induced neuronal death, and attenuate viral replication. BM‐EVs treatment upregulated interferon‐stimulated genes. Flow cytometry analysis revealed a reduction in the frequency of macrophages. At the same time, CD4+ T cells and neutrophils were significantly augmented, accompanied by the alteration of cytokine expression with the administration of BM‐EVs, reinforcing the immunomodulatory role of EVs during JEV‐induced encephalitis. In conclusion, our study describes the beneficial role of BM‐EVs in limiting JEV pathology by attenuating virus replication, enhancing antiviral response, and neurogenesis in primary neuronal stem cells. However, BM‐EVs do not seem to protect BBB integrity and alter immune cell infiltration into the treated brain.
Suchi Gupta, Vishnu Krishnakumar, Naina Soni, E Pranshu Rao, Arup Banerjee, and Sujata Mohanty
Elsevier BV
Lucky Sarkar, Lauren Oko, Soham Gupta, Andrew N. Bubak, Bishnu Das, Parna Gupta, Abass Alao Safiriyu, Chirag Singhal, Ujjwal Neogi, David Bloom,et al.
Elsevier BV
Suchi Gupta, Pinky, Vishal, Harshita Sharma, Naina Soni, E Pranshu Rao, Manu Dalela, Alka Yadav, Nidhi Nautiyal, Anupam Kumar,et al.
Springer Science and Business Media LLC
Naina Soni, Suchi Gupta, Surender Rawat, Vishnu Krishnakumar, Sujata Mohanty, and Arup Banerjee
MDPI AG
Adult Mesenchymal stem cells-derived exosomes carry several biologically active molecules that play prominent roles in controlling disease manifestations. The content of these exosomes, their functions, and effect on the immune cells may differ depending on their tissue sources. Therefore, in this study, we purified the exosomes from three different sources and, using the RNA-Seq approach, highly abundant microRNAs were identified and compared between exosomes and parental cells. The effects of exosomes on different immune cells were studied in vitro by incubating exosomes with PBMC and neutrophils and assessing their functions. The expression levels of several miRNAs varied within the different MSCs and exosomes. Additionally, the expression profile of most of the miRNAs was not similar to that of their respective sources. Exosomes isolated from different sources had different abilities to induce the process of neurogenesis and angiogenesis. Moreover, these exosomes demonstrated their varying effect on PBMC proliferation, neutrophil survival, and NET formation, highlighting their versatility and broad interaction with immune cells. The knowledge gained from this study will improve our understanding of the miRNA landscape of exosomes from hMSCs and provide a resource for further improving our understanding of exosome cargo and their interaction with immune cells.
Aarti Tripathi, Bhupendra Singh Rawat, Sankar Addya, Milan Surjit, Prafullakumar Tailor, Sudhanshu Vrati, and Arup Banerjee
American Society for Microbiology
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.
Aarti Tripathi, Arup Banerjee, and Sudhanshu Vrati
The Company of Biologists
ABSTRACT A mouse-adapted isolate of Japanese encephalitis virus (JEV), designated as JEV-S3, was generated by serially passaging the P20778 strain of the virus in 3- to 4-week-old C57BL/6 mice. Blood-brain barrier leakage was evident in JEV-S3-infected mice, in which viral antigens and RNA were consistently demonstrated in the brain, along with infiltration of activated immune cells, as evidenced by an increased CD45+CD11b+ cell population. Histopathology studies showed the presence of perivascular cuffing, haemorrhage and necrotic foci in the virus-infected brain, conforming to the pathological changes seen in the brain of JEV-infected patients. Mass spectrometry studies characterized the molecular events leading to brain inflammation in the infected mice. Notably, a significant induction of inflammatory cytokines, such as IFNγ, IL6, TNFα and TGFβ, was observed. Further, genome sequencing of the JEV-S3 isolate identified the mutations selected during the mouse passage of the virus. Overall, we present an in-depth characterization of a robust and reproducible mouse model of JEV infection. The JEV-S3 isolate will be a useful tool to screen antivirals and study virus pathogenesis in the adolescent mouse model.
Surender Rawat, Sudhanshu Vrati, and Arup Banerjee
Elsevier BV
Kiran Bala Sharma, Simran Chhabra, Suruchi Aggarwal, Aarti Tripathi, Arup Banerjee, Amit Kumar Yadav, Sudhanshu Vrati, and Manjula Kalia
Microbiology Society
Advances in proteomics have enabled a comprehensive understanding of host–pathogen interactions. Here we have characterized Japanese encephalitis virus (JEV) infection-driven changes in the mouse embryonic fibroblast (MEF) proteome. Through tandem mass tagging (TMT)-based mass spectrometry, we describe changes in 7.85 % of the identified proteome due to JEV infection. Pathway enrichment analysis showed that proteins involved in innate immune sensing, interferon responses and inflammation were the major upregulated group, along with the immunoproteasome and poly ADP-ribosylation proteins. Functional validation of several upregulated anti-viral innate immune proteins, including an active cGAS–STING axis, was performed. Through siRNA depletion, we describe a crucial role of the DNA sensor cGAS in restricting JEV replication. Further, many interferon-stimulated genes (ISGs) were observed to be induced in infected cells. We also observed activation of TLR2 and inhibition of TLR2 signalling using TLR1/2 inhibitor CU-CPT22-blocked production of inflammatory cytokines IL6 and TNF-α from virus-infected N9 microglial cells. The major proteins that were downregulated by infection were involved in cell adhesion (collagens), transport (solute carrier and ATP-binding cassette transporters), sterol and lipid biosynthesis. Several collagens were found to be transcriptionally downregulated in infected MEFs and mouse brain. Collectively, our data provide a bird’s-eye view into how fibroblast protein composition is rewired following JEV infection.
Atoshi Banerjee, Aarti Tripathi, Shweta Duggal, Arup Banerjee, and Sudhanshu Vrati
Springer Science and Business Media LLC
AbstractDengue virus (DENV) infection causes dengue fever in humans, which can lead to thrombocytopenia showing a marked reduction in platelet counts, and dengue hemorrhagic fever. The virus may cause thrombocytopenia either by destroying the platelets or by interfering with their generation via the process of megakaryopoiesis. MEG-01 is the human megakaryoblastic leukemia cell line that can be differentiated in vitro by phorbol-12-myristate-13-acetate (PMA) treatment to produce platelet-like-particles (PLPs). We have studied DENV infection of MEG-01 cells to understand its effect on megakaryopoiesis and the generation of PLPs. We observed that DENV could infect only naive MEG-01 cells, and differentiated cells were refractory to virus infection/replication. However, DENV-infected MEG-01 cells, when induced for differentiation with PMA, supported an enhanced viral replication. Following the virus infection, the MEG-01 cells showed a marked reduction in the surface expression of platelet markers (CD41, CD42a, and CD61), a decreased polyploidy, and significantly reduced PLP counts. DENV infection caused an enhanced Notch signaling in MEG-01 cells where the virus envelope protein was shown to interact with TAL-1, a host protein important for megakaryopoiesis. These observations provide new insight into the role of DENV in modulating the megakaryopoiesis and platelet production process.
Jaya Saini, Bhaswati Bandyopadhyay, Abhay Deep Pandey, V. G. Ramachandran, Shukla Das, Vikas Sood, Arup Banerjee, and Sudhanshu Vrati
American Society for Microbiology
Dengue virus (DENV) infection usually causes dengue fever (DF) with flu-like illness affecting infants, young children, and adults. The DF occasionally evolves into a potentially lethal complication called dengue severe (DS) leading to a rapid fall in platelet count along with plasma leakage, fluid accumulation, respiratory distress, and severe bleeding. The diverse clinical spectrum of dengue disease, as well as its significant similarity to other febrile viral illnesses, makes early identification more challenging in this high-risk group. microRNAs (miRNAs) are small (∼19 to 21 nucleotides [nt] in length), noncoding RNAs, extremely stable and easily detectable in the plasma; thus, they have potential as biomarkers for diagnosing and monitoring human diseases. This study provides a comprehensive analysis of miRNAs circulating in plasma of dengue virus-infected patients and identifies the miRNA signatures that have biomarker potential for dengue infection and disease progression.
Arup Banerjee and Aarti Tripathi
F1000 Research Ltd
Japanese encephalitis (JE) is a clinical manifestation of the brain inflammation caused by JE virus (JEV). This virus imparts permanent neurological damage, thus imposing a heavy burden on public health and society. Neuro-inflammation is the hallmark of JEV infection. The prolonged pro-inflammatory response is due primarily to microglial activation, which eventually leads to severe encephalitis. A continual effort is going on in the scientific community toward an understanding of cellular and molecular factors that are involved in JEV neuro-invasion and inflammatory processes. This review not only gives a comprehensive update on the recent advances on understanding virus structure and mechanisms of pathogenesis but also briefly discusses crucial unresolved issues. We also highlight challenging areas of research that might open new avenues for controlling virus-induced neuro-inflammation.
Sriparna Mukherjee, Irshad Akbar, Bharti Kumari, Sudhanshu Vrati, Anirban Basu, and Arup Banerjee
Wiley
AbstractMicroRNAs (miRNAs) released from the activated microglia upon neurotropic virus infection may exacerbate the neuronal damage. Here, we identified let‐7a and let‐7b (let‐7a/b) as one of the essential miRNAs over‐expressed upon Japanese Encephalitis virus (JEV) infection and released in the culture supernatant of the JEV‐infected microglial cells through extracellular vesicles. The let‐7a/b was previously reported to modulate inflammation in microglial cells through Toll‐like receptor 7 (TLR7) pathways; although their role in accelerating JEV pathogenesis remain unexplored. Therefore, we studied the role of let‐7a/b in modulating microglia‐mediated inflammation during JEV infection and investigated the effect of let‐7a/b‐containing exosomes on primary neurons. To this end, we examined let‐7a/b and NOTCH signaling pathway in TLR7 knockdown (KD) mice. We observed that TLR7 KD or inhibition of let‐7a/b suppressed the JEV‐induced NOTCH activation possibly via NF‐κB dependent manner and subsequently, attenuated JEV‐induced TNFα production in microglial cells. Furthermore, exosomes secreted from let‐7a/b over‐expressed microglia when transferred to uninfected mice brain induced caspase activation. Exosomes secreted from virus‐infected or let‐7a/b over‐expressed microglia when co‐incubated with mouse neuronal (Neuro2a) cells or primary cortical neurons also facilitated caspase activation leading to neuronal death. Thus, our results provide evidence for the multifaceted role of let‐7a/b miRNAs in JEV pathogenesis. Let‐7a/b can interact with TLR7 and NOTCH signaling pathway and enhance TNFα release from microglia. On the other hand, the exosomes secreted by JEV‐infected microglia can activate caspases in uninfected neuronal cells which possibly contribute to bystander neuronal death. image Cover Image for this issue: doi: 10.1111/jnc.14506.
Himani Sharma, Aarti Tripathi, Bharti Kumari, Sudhanshu Vrati, and Arup Banerjee
Mary Ann Liebert Inc
Artificial microRNA (amiRNA)-mediated inhibition of viral replication has recently gained importance as a strategy for antiviral therapy. In this study, we evaluated the benefit of using the amiRNA vector against Japanese encephalitis virus (JEV). We designed three single amiRNA sequences against the consensus sequence of 3′ untranslated region (3′UTR) of JEV and tested their efficacy against cell culture-grown JEV Vellore strain (P20778) in neuronal cells. The binding ability of three amiRNAs on 3′UTR region was tested in vitro in HEK293T cells using a JEV 3′UTR tagged with luciferase reporter vector. Transient transfection of amiRNAs was nontoxic to cells as evident from the MTT assay and caused minimal induction in interferon-stimulated gene expression. Furthermore, our result suggested that transient expression of two amiRNAs (amiRNA #1 and amiRNA #2) significantly reduced intracellular viral RNA and nonstructural 1 (NS1) protein, as well as diminished infectious viral particle release up to 95% in the culture supernatant as evident from viral plaque reduction assay. Overall, our results indicated that RNA interference based on amiRNAs targeting viral conserved regions at 3′UTR was a useful approach for improvements of nucleic acid inhibitors against JEV.
Abhay Deep Pandey, Saptamita Goswami, Shweta Shukla, Shaoli Das, Suman Ghosal, Manisha Pal, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Nandita Basu, Vikas Sood,et al.
Elsevier BV
Arup Banerjee, Shweta Shukla, Abhay Deep Pandey, Saptamita Goswami, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Shukla Das, Arjun Malhotra, Amitesh Agarwal, Srima Adhikari,et al.
Elsevier BV
Saptamita Goswami, Atoshi Banerjee, Bharti Kumari, Bhaswati Bandopadhyay, Nemai Bhattacharya, Nandita Basu, Sudhanshu Vrati, and Arup Banerjee
Springer Science and Business Media LLC
Manikankana Bandopadhyay, Neelakshi Sarkar, Sibnarayan Datta, Dipanwita Das, Ananya Pal, Rajesh Panigrahi, Arup Banerjee, Chinmay K. Panda, Chandrima Das, Shekhar Chakrabarti,et al.
Springer Science and Business Media LLC
Bharti Kumari, Pratistha Jain, Shaoli Das, Suman Ghosal, Bibhabasu Hazra, Ashish Chandra Trivedi, Anirban Basu, Jayprokas Chakrabarti, Sudhanshu Vrati, and Arup Banerjee
Springer Science and Business Media LLC
AbstractMicroglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation.