People : Scientific : Faculty & Scientists

DR. MANJULA KALIA, Ph.D. 

Research Scientist E
+91-129-2876323 
manjula [at] thsti [dot] res [dot] in
Ph.D., National Institute of Immunology, Aruna Asaf Ali Marg,New. Delhi- 110 067, INDIA
M.Sc. (Biotechnology), M.S. University, Baroda, Gujarat, INDIA
B.Sc (Botany Hons.), Hindu College, Delhi University, INDIA,

RESEARCH INTEREST

AUTOPHAGY IN VIRUS INFECTION AND IMMUNE RESPONSE

Host-pathogen interaction is a series of complex and intertwined cellular and signalling events that determine disease outcome. Understanding these interactions is crucial for identification and development of therapies, vaccines and anti-viral drugs. The research focus of my group is to understand how Flaviviruses (positive-stranded RNA viruses- prototype Japanese Encephalitis Virus and Dengue virus) modulate the host autophagy and membrane trafficking pathways for their pathogenesis.

Autophagy is a cellular degradative pathway that maintains cellular homeostasis. Several viruses lead to upregulation of autophagy in infected cells which is closely related to their pathogenesis. However, the role of autophagy in virus infection is still incompletely understood and controversial.

Recent studies in our laboratory have characterized autophagic progression during JEV infection and have shown that autophagy is primarily anti-viral. We have also shown that the autophagosomal protein LC3 plays a crucial autophagy independent role as part of the JEV replication complex.

The current research themes of our lab are-

Regulation and enhancement of immune responses to flavivirus infections by autophagy modulation. Autophagy is an important component of the innate and adaptive immune response against a variety of viral and bacterial pathogens. We are currently investigating the mechanisms of recognition of viral elements by RLRs and TLRs in the context of functional vs dysfunctional autophagy pathway and its effect on activation of interferon stimulated genes and interferon secretion. We are also studying whether autophagy can modulate activation of dendritic cells for cytokine responses and for activation of T cells. Our research that is currently being performed with primary human dendritic cells will further be extended into animal models of disease.

Molecular Regulation of Autophagy during virus infection. The various stimuli that activate autophagy mainly converge upon the mammalian target of rapamycin (mTOR), an evolutionarily conserved threonine kinase that integrates signals from nutrients and growth factors for the regulation of many cellular processes. We are investigating how mTOR signalling pathways and cellular stress responses such as oxidative stress and ER stress modulate autophagy induction during flavivirus infections.

Mechanisms of anti-viral role of autophagy.  Autophagy regulation controls the maturation of autophagosomes into degradative autolysosomes which is coordinately regulated by endosomal and autophagy protein complexes. We observe that autophagy restricts virus replication at early stages of infection however it becomes dysfunctional as infection progresses leading to lysosomal dysfunction and ultimately cell death. We are investigating how the components of general and selective autophagy play an anti-viral role. We are also characterizing how the virus counters autophagic degradation (inhibition of autophagosomal-lysosomal fusion, lysosomal membrane permeabilization) and its possible link to neurodegeneration and neuronal cell death. We observe significant cross talk between autophagic and apoptotic pathway and are attempting to understand how autophagy in response to virus infection can regulate apoptosis and virus propagation from infected cells.

  • Manish Sharma, Sankar Bhattacharyya, Kiran Bala Sharma, Shailendra Chauhan, Suramya Asthana, M. Z. Abdin, Sudhanshu Vrati and Manjula Kalia (2017) "Japanese encephalitis virus activates autophagy through XBP1 and ATF6 ER stress sensors in neuronal cells" Journal of General Virology 2017 May 23. doi: 10.1099/jgv.0.000792. [Epub ahead of print]
  • Minu Nain, Sriparna Mukherjee, Sonali Porey Karmakar, Adrienne W. Paton, James C. Paton, M.Z. Abdin, Anirban Basu, Manjula Kalia, Sudhanshu Vrati (2017) "GRP78 is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells" Journal of Virology Feb 28;91(6). pii: e02274-16. doi: 10.1128/JVI.02274-16. Print 2017 Mar 15
  • Daniel J. Klinosky et al., Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) Autophagy 2016 Jan 2:12(1): 1-222.
  • Minu Nain, M.Z.Abdin, Manjula Kalia* and Sudhanshu Vrati* (2016) “Japanese encephalitis virus invasion of cell: allies and alleys” Reviews in Medical Virology Mar; 26(2):129-41. doi:10.1002/rmv.1868 [Epub 2015 Dec 23] [*Co-corresponding Author]
  • Nimesh Gupta, Melissanne de Wispelaere, Maxime Lecerf, Manjula Kalia, Tobias Scheel, Sudhanshu Vrati, Claudia Berek, Srinivas V. Kaveri, Philippe Despres, Sebastien Lacroix-Desmazes, Jordan D. Dimitrov (2015) “Neutralization of Japanese Encephalitis Virus by heme-induced broadly reactive human monoclonal antibody” Scientific Reports. 2015 Nov6:5:16248. Doi: 10.1038/srep16248.
  • Deepika Bhullar, Richa Jalodia, Manjula Kalia, Sudhanshu Vrati (2014) “Cytoplasmic Translocation of Polypyrimidine Tract-Binding Protein and Its Binding to Viral RNA during Japanese Encephalitis Virus Infection Inhibits Virus Replication” PLoS ONE 9(12):e114931. doi:10.1371/journal.pone.0114831. eCollection 2014
  • Manish Sharma, Sankar Bhattacharyya, Minu Nain, Manpreet Kaur, Vikas Sood, Vishal Gupta, Renu Khasa, Malik Abdin, Sudhanshu Vrati and Manjula Kalia (2014) “Japanese Encephalitis Virus Replication is Negatively Regulated by Autophagy and Occurs on LC3-I- and EDEM1-containing Membranes”. Autophagy. 2014 Sep; 10(9): 1637-51. Doi: 10.4161/auto.29455. Epub 2014 July16.
  • Nimesh Gupta, Pushpa Hegde, Maxime Lecerf, Minu Nain, Manpreet Kaur, Manjula Kalia, Sudhanshu Vrati, Jagadeesh Bayry, Sebastien Lacroix-Desmazes and Srini V. Kaveri (2014) “Japanese encephalitis virus expands regulatory T cells by increasing the expression of PD-L1 on dendritic cells” Eur.J.Immunol. 2014 May;44(5):1363-74. [Epub 2014 Mar24]
  • Manjula Kalia*, Renu Khasa, Manish Sharma, Minu Nain and Sudhanshu Vrati (2013) “Japanese Encephalitis Virus Infects Neuronal Cells through a Clathrin Independent Endocytic Mechanism” Journal of Virology. 2013 Jan; 87(1):148-162. [Epub 2012 Oct 10]. [*Corresponding Author]
  • Vivek Chandra, Manjula Kalia, Krishan Hajela and Shahid Jameel (2010) “The The ORF3 protein of hepatitis E virus delays degradation of activated growth factor receptors by interacting with CIN85 and blocking formation of the Cbl-CIN85 complex” Journal of Virology. 2010 Apr; 84(8):3857-67. [Epub 2010 Feb 3].
  • Manjula Kaliaand Shahid Jameel (2011) Virus entry paradigms. Amino Acids Nov; 41(5):1147-57. [Epub 2009 Oct 15]. Review.
  • Manjula Kalia*, Vivek Chandra, Sheikh Abdul Rahman, Deepak Sehgal and Shahid Jameel (2009) “Heparan Sulfate Proteoglycans are Required for Cellular Binding of the Hepatitis E Virus ORF2 Capsid Protein and for Viral Infection” Journal of Virology Vol 83, No24:12714-24 [Epub 2009 Oct7]. [*Corresponding Author]
  • Vivek Chandra, Shikha Taneja, Manjula Kalia and Shahid Jameel (2008) “Molecular Biology and Pathogenesis of Hepatitis E Virus” Journal of Biosciences 33:451-64.
  • Manjula Kalia, Sudha Kumari, Rahul Chadda, Michelle M. Hill, Robert G. Parton, and Satyajit Mayor (2006)“Arf6-independent GEECs fuse with sorting endosomes via a Rab5/PI-3’ kinase dependent machinery” Mol Biol Cell 17: 3689-3704
  • M. Awasthi-Kalia, K.V. Bhat and R.K. Anand. (2002) “Genetic characterization of Mus musculus and related forms from India”. Experimental Animals 51: No 1. 103-107
  • M. Mishra, N. Dubey, S.M. Totey, K.V. Bhat, S. Babu, M. Awasthi-Kaliaand R.K. Anand. (2002) “Phylogenetic relationships and genetic polymorphisms in wild Indian mice”. Biomolecular Engineeering 18: No 6. 281-288.
  • M. Awasthi-Kalia, P.P.M. Schnetkamp and J.P. Deans. (2001). “Differential effects of Filipin and Methyl-b-cyclodextrin on B Cell Receptor Signaling”. Biochemical and Biophysical Research Communications 287: 77-82.
  • R.J. Petrie, P.P.M. Schnetkamp, K.D. Patel, M. Awasthi-Kalia and J.P. Deans. (2000) "Transient Translocation of the B Cell Receptor and Src Homology 2 Domain- Containing Inositol Phosphatase to Lipid Rafts: Evidence Toward a Role in Calcium Regulation". Journal of Immunology. 165: 1220-1227.
  • M. Awasthi, K.V. Bhat and R.K. Anand. (1999) "Allozyme variation in four Indian species of genus Mus: A comparative analysis ". Journal of Genetics. 78: No 2. 73-80.
  • M. Awasthi, S. Rath, P.A. Cazenave and R.K. Anand. (1999) "TCR Vb17 gene polymorphism in the Indian Mus musculus". Journal of Biosciences. 24: 163-169.
  • M. Awasthi, K.V. Bhat and R.K. Anand. (1998) "Genetic heterogeneity in the Indian Mus musculus". Biochemical Genetics. 36: Nos. 7/8 245-258.

MS. RENU KHASA
SENIOR RESEARCH FELLOW

MS. KIRAN BALA
PH.D STUDENT

MR. SHAILENDRA CHAUHAN
PH.D STUDENT

MS. RIYA SARKAR
PH.D STUDENT

DR. ANSHU AGARWAL
RESEARCH ASSOCIATE