FACULTY / ARINDAM MONDAL
Molecular Virology Laboratory
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Influenza Virus Ribonucleoprotein Complex
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Influenza viruses are segmented negative sense RNA virus where eight different genomic RNA segments constitutes eight ribonucleoprotein complexes (RNPs). Each genomic RNA segment is enwrapped with multiple copies of viral nucleoproteins (NP) in their oligomeric form, and associates with a single copy of heterotrimeric RNA polymerase (RdRp), composed of three different viral proteins, PB1, PB2 and PA. Extensive protein-protein and RNA-protein interactions between these components results in double helical, hairpin like structures that are characteristic for all influenza virus RNPs. Viral RNPs drive viral transcription and replication during different stages of virus life cycle and interact with a large number of host factors which modulate these processes. Yet, how different components of RNPs dynamically assemble to form these macromolecular complexes is largely unknown. We implement biochemical and biophysical approaches to characterize the molecular interactions between various viral and host factors that play key role in RNP assembly process. |
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Phosphorylation is a reversible post translational modification of proteins that adds negatively charged phosphate moiety to specific serine, threonine or tyrosine residues. This can alter target proteins by inducing conformational change, creating docking site for other proteins and causing intracellular relocation. Viral proteins also undergo reversible phosphorylation which can have major impacts on viral infection, replication, and cytotoxicity in a host cell. For many medically relevant viruses, there is now considerable evidence that both viral and cellular kinases play important roles in viral infection. RNA viruses, however, does not known to encode any kinase activity and hence relies exclusively upon host kinases for phosphorylation of viral proteins. Recent advancements with influenza A viruses presented strong evidence in support of the role of host kinases in regulating assembly of viral RNPs and their activity in gene transcription and genome replication. We are interested in identifying RNP associated host kinases that might play key role viral RNA synthesis. Using a combination of proteomics and genomics approaches we try to characterize role of pro-viral host kinases in establishing the infection of influenza and other RNA viruses. |
Screening small molecule library for anti-viral drug development
Apart from our interest in understanding the molecular basis of RNP assembly and their interaction with various host factors, we are also focused upon targeting these virus-host interactions to develop novel anti-viral therapies. Currently we are trying to develop a split reporter based assay system to monitor the virus-host interaction in live cells. Once standardized, such assay system could be utilized to setup a high-throughput screening platform in order to identify drugs with anti-viral activity.
Lab Members
- Saptarshi Banerjee; PhD Scholar (JRF, CSIR-NET)
- Nandita Kedia (JRF, CSIR-NET)
- Dipon Saha; Project intern, Integrated MSc-PhD program in Chemical and Molecular Biology, IIT KGP & IACS
- Jonathan Divito, SN Bose Fellow, University of Wisconsin Madison
- Anupam Bhoy; Summer intern (2017), IISER Pune
Publications
Mondal A, Dawson AR, Potts GK, Freiberger EC, Baker SF, Moser LA, Bernard KA, Coon JJ, Mehle A. Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery. Elife. 2017 Jul 31;6. pii: e26910. doi: 10.7554/eLife.26910. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28758638
Kirui J, Mondal A, Mehle A. Ubiquitination up-regulates influenza virus polymerase function. J Virol. 2016 Sep 28. pii:JVI.0182916[Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27681127
Mondal A, Potts GK, Dawson AR, Coon JJ, Mehle A. Phosphorylation at the homotypic interface regulates nucleoprotein oligomerization and assembly of the influenza virus replication machinery. PLoS Pathogens. 2015 Apr 13;11(4):e1004826. http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004826
Chakraborty A, Bera A, Mukherjee A, Basak P, Khan I, Mondal A, Roy A, Bhattacharyya A, SenGupta S, Roy D, Nag S, Ghosh A, Chattopadhyay D, Bhattacharyya M. Changing bacterial profile of Sundarbans, the world heritage mangrove: Impact of anthropogenic interventions. World Journal Microbiol Biotechnol. 2015 Apr;31(4):593 610. http://link.springer.com/article/10.1007%2Fs11274-015-1814-5
Mondal A, Victor KG, Pudupakam RS, Lyons CE, Wertz GW. Newly identified phosphorylation site in the vesicular stomatitis virus P protein is required for viral RNA synthesis. Journal of Virology. 2014 Feb;88(3):1461-72 http://jvi.asm.org/content/88/3/1461.full
Mondal A, Roy A, Sarkar S, Mukherjee J, Ganguly T, Chattopadhyay D. Interaction of chandipura virus N and P proteins: identification of two mutually exclusive domains of N involved in interaction with P. PLoS One. 2012;7(4):e34623. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034623
Mondal A, Bhattacharya R, Ganguly T, Mukhopadhyay S, Basu A, Basak S, Chattopadhyay D. Elucidation of functional domains of Chandipura virus Nucleocapsid protein involved in oligomerization and RNA binding: implication in viral genome encapsidation Virology. 2010 Nov 10;407(1):33-42. http://www.sciencedirect.com/science/article/pii/S0042682210004861
Chattopadhyay T, Mukherjee M, Mondal A, Maiti P, Banerjee A, Banu KS, Bhattacharya S, Roy B, Chattopadhyay DJ, Mondal TK, Nethaji M, Zangrando E, Das D. A unique nickel system having versatile catalytic activity of biological significance. Inorganic Chemistry. 2010 Apr 5;49(7):3121-9. http://pubs.acs.org/doi/abs/10.1021/ic901546t
Mandal S, Castiñeiras A, Mondal TK, Mondal A, Chattopadhyay D, Goswami S. An unusual (H(2)O)(20) discrete water cluster in the supramolecular host of a charge transfer platinum(ii) complex: cytotoxicity and DNA cleavage activities. Dalton Trans. 2010 Oct 28;39(40):9514-22. * Cover page article http://pubs.rsc.org/en/Content/ArticleLanding/2010/DT/c0dt00527d
Basak S, Mondal A, Polley S, Mukhopadhyay S, Chattopadhyay D. Reviewing Chandipura: a vesiculovirus in human epidemics. Biosci Rep. 2007 Oct; 27(4-5):275-98. http://www.bioscirep.org/content/27/4-5/275
Book Chapter:
Ganguly T, Polley S, Mandal A, Roy A, Chattopadhyay D. Understanding Chandipura virus: identification of a potential drug target. New Horizon in Biotechnology 2008.
Mondal A, Dawson AR, Potts GK, Freiberger EC, Baker SF, Moser LA, Bernard KA, Coon JJ, Mehle A. Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery. Elife. 2017 Jul 31;6. pii: e26910. doi: 10.7554/eLife.26910. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28758638
Kirui J, Mondal A, Mehle A. Ubiquitination up-regulates influenza virus polymerase function. J Virol. 2016 Sep 28. pii:JVI.0182916[Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27681127
Mondal A, Potts GK, Dawson AR, Coon JJ, Mehle A. Phosphorylation at the homotypic interface regulates nucleoprotein oligomerization and assembly of the influenza virus replication machinery. PLoS Pathogens. 2015 Apr 13;11(4):e1004826. http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004826
Chakraborty A, Bera A, Mukherjee A, Basak P, Khan I, Mondal A, Roy A, Bhattacharyya A, SenGupta S, Roy D, Nag S, Ghosh A, Chattopadhyay D, Bhattacharyya M. Changing bacterial profile of Sundarbans, the world heritage mangrove: Impact of anthropogenic interventions. World Journal Microbiol Biotechnol. 2015 Apr;31(4):593 610. http://link.springer.com/article/10.1007%2Fs11274-015-1814-5
Mondal A, Victor KG, Pudupakam RS, Lyons CE, Wertz GW. Newly identified phosphorylation site in the vesicular stomatitis virus P protein is required for viral RNA synthesis. Journal of Virology. 2014 Feb;88(3):1461-72 http://jvi.asm.org/content/88/3/1461.full
Mondal A, Roy A, Sarkar S, Mukherjee J, Ganguly T, Chattopadhyay D. Interaction of chandipura virus N and P proteins: identification of two mutually exclusive domains of N involved in interaction with P. PLoS One. 2012;7(4):e34623. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034623
Mondal A, Bhattacharya R, Ganguly T, Mukhopadhyay S, Basu A, Basak S, Chattopadhyay D. Elucidation of functional domains of Chandipura virus Nucleocapsid protein involved in oligomerization and RNA binding: implication in viral genome encapsidation Virology. 2010 Nov 10;407(1):33-42. http://www.sciencedirect.com/science/article/pii/S0042682210004861
Chattopadhyay T, Mukherjee M, Mondal A, Maiti P, Banerjee A, Banu KS, Bhattacharya S, Roy B, Chattopadhyay DJ, Mondal TK, Nethaji M, Zangrando E, Das D. A unique nickel system having versatile catalytic activity of biological significance. Inorganic Chemistry. 2010 Apr 5;49(7):3121-9. http://pubs.acs.org/doi/abs/10.1021/ic901546t
Mandal S, Castiñeiras A, Mondal TK, Mondal A, Chattopadhyay D, Goswami S. An unusual (H(2)O)(20) discrete water cluster in the supramolecular host of a charge transfer platinum(ii) complex: cytotoxicity and DNA cleavage activities. Dalton Trans. 2010 Oct 28;39(40):9514-22. * Cover page article http://pubs.rsc.org/en/Content/ArticleLanding/2010/DT/c0dt00527d
Basak S, Mondal A, Polley S, Mukhopadhyay S, Chattopadhyay D. Reviewing Chandipura: a vesiculovirus in human epidemics. Biosci Rep. 2007 Oct; 27(4-5):275-98. http://www.bioscirep.org/content/27/4-5/275
Book Chapter:
Ganguly T, Polley S, Mandal A, Roy A, Chattopadhyay D. Understanding Chandipura virus: identification of a potential drug target. New Horizon in Biotechnology 2008.
