- M.Sc., School of Biosciences, Mahatma Gandhi University, India
- Ph.D., School of Biotechnology Madurai Kamaraj University, India
- Postdoctoral Fellow, Purdue University, Indiana
Program or Department Affiliations
|BMMB Graduate Program||Molecular, Cellular, and Integrative Biosciences|
Virus-host interactions involved in the pathogenesis of alphaviruses and flaviviruses. Analysis of virus-induced structures and cytoskeletal modifications in mammalian host and insect vector using high-resolution live-cell imaging and electron microscopy. Viral determinants of neurotropism, encephalitis, transmission, and persistence in BSL-3 pathogens.
Research in my laboratory is mainly focused on understanding the molecular mechanisms involved in the replication and assembly of flaviviruses and alphaviruses. We use molecular virology, live-cell imaging, super-resolution microscopy, and electron microscopy to elucidate the viral and host determinants of viral RNA genome replication and packaging. Our goal is to study the virus-host and virus-vector interactions in vivo to characterize the factors that determine the host range, transmission, virulence, and persistence at the molecular level. This research will lead to understanding the molecular basis of virus assembly and pathogenesis that will facilitate the identification of targets for antivirals and vaccine candidates against these dangerous human pathogens.
Alphaviruses and flaviviruses are vector-borne, enveloped, positive-strand RNA viruses from the Togaviridae and Flaviviridae family, respectively. Infectious diseases caused by many of these arthropod-borne viruses (arboviruses) remain an international public health concern as there are no vaccines, prophylactic, or treatments against these human pathogens. Virus-vector interactions and vector-pathogen adaptation to climate variability play essential roles in the emergence and transmission of infectious diseases caused by these viruses. Our lab investigates the virus-host and virus-vector interactions that facilitate virus entry, modification of the host system for virus replication, and dissemination. Using BSL-2 and BSL-3 viruses such as West Nile, dengue, Zika, Sindbis, western equine encephalitis, and chikungunya, we aim to investigate the molecular pathogenesis and transmission in mouse models and live mosquitoes. Our long-term goals are to understand the molecular details of the virus life cycle, and design and develop new strategies to perturb them to control and combat these pathogens.
Spatio-temporal dynamics of alphavirus and flavivirus replication and assembly in mosquito and mammalian cells
Our group is building upon our foundational research on live-cell imaging of alphavirus replication and assembly. We are going to expand this research area using modified RNA and protein components of Chikungunya, West Nile, dengue, and Zika virus. Utilizing molecular virology, live-cell imaging, super-resolution microscopy, and electron microscopy techniques, we are aiming to achieve a high spatial and temporal resolution of cellular processes in the context of an invading pathogen. Information obtained from these studies will help to understand how spatial and temporal differences of host and viral components affect different disease outcomes in mammalian host and arthropod vector.
Cytoskeletal modification and virus-induced structures associated with viral RNA replication
Many positive-strand RNA viruses manipulate the hosts with multi-functional proteins encoded in their relatively small genome. These viruses also evade the immune system by a myriad of techniques and cause diseases such as arthralgia, encephalitis, and hemorrhagic fever. We are interested in mapping the host cellular pathways that are impacted by virus replication to elucidate how positive-strand RNA viruses hijack cellular pathways to complete the virus lifecycle efficiently. Specifically, we are interested in understanding how cytoskeleton modification occurs and how that affects virus cell-to-cell transport and antibody neutralization. The crosstalk between virus replication components and the host factors that restrict virus replication will help to identify new targets for antivirals.
Understanding viral determinants of neurotropism, encephalitis, and persistence
We are planning to unravel the molecular processes involved in virus-receptor engagement during entry and host pathways that restrict virus replication. These studies are aimed at establishing the role of alphavirus and flavivirus envelope proteins in determining neurotropism, neurovirulence, cytopathicity, and neuronal persistence. We are using BSL-2 and BSL-3 level neurotropic and encephalitic arboviruses, including West Nile virus and western equine encephalitis, to unravel molecular pathways in infected neuronal cells that lead to cell death, viral clearance or persistence. Additionally, we are interested in modifying neurotropic viruses to be used as tools to probe various host pathways in neurons.
- Kaur R, Neetu, Mudgal R, Jose J, Kumar P, Tomar S. Glycan-dependent chikungunya viral infection divulged by antiviral activity of NAG specific chi-like lectin. Virology. 2019 Jan 2;526:91-98. doi: 10.1016/j.virol.2018.10.009. Epub 2018 Oct 25. PubMed PMID: 30388630.
- Gizzi AS, Grove TL, Arnold JJ, Jose J, Jangra RK, Garforth SJ, Du Q, Cahill SM, Dulyaninova NG, Love JD, Chandran K, Bresnick AR, Cameron CE, Almo SC. A naturally occurring antiviral ribonucleotide encoded by the human genome. Nature. 2018 Jun;558(7711):610-614. doi: 10.1038/s41586-018-0238-4. Epub 2018 Jun 20. PubMed PMID: 29925952; PubMed Central PMCID: PMC6026066.
- Jose J, Taylor AB, Kuhn RJ. Spatial and Temporal Analysis of Alphavirus Replication and Assembly in Mammalian and Mosquito Cells. MBio. 2017 Feb 14;8(1). doi: 10.1128/mBio.02294-16. PubMed PMID: 28196962; PubMed Central PMCID: PMC5312085.
- Jose J, Tang J, Taylor AB, Baker TS, Kuhn RJ. Fluorescent Protein-Tagged Sindbis Virus E2 Glycoprotein Allows Single Particle Analysis of Virus Budding from Live Cells. Viruses. 2015 Nov 27;7(12):6182-99. doi: 10.3390/v7122926. PubMed PMID: 26633461; PubMed Central PMCID: PMC4690852.
- Akey DL, Brown WC, Jose J, Kuhn RJ, Smith JL. Structure-guided insights on the role of NS1 in flavivirus infection. Bioessays. 2015 May;37(5):489-94. doi: 10.1002/bies.201400182. Epub 2015 Mar 11. PubMed PMID: 25761098; PubMed Central PMCID: PMC4409125.
- Porta J, Jose J, Roehrig JT, Blair CD, Kuhn RJ, Rossmann MG. Locking and blocking the viral landscape of an alphavirus with neutralizing antibodies. J Virol. 2014 Sep 1;88(17):9616-23. doi: 10.1128/JVI.01286-14. Epub 2014 Jun 11. PubMed PMID: 24920796; PubMed Central PMCID: PMC4136364.
- Akey DL, Brown WC, Dutta S, Konwerski J, Jose J, Jurkiw TJ, DelProposto J, Ogata CM, Skiniotis G, Kuhn RJ, Smith JL. Flavivirus NS1 structures reveal surfaces for associations with membranes and the immune system. Science. 2014 Feb 21;343(6173):881-5. doi: 10.1126/science.1247749. Epub 2014 Feb 6. PubMed PMID: 24505133; PubMed Central PMCID: PMC4263348.
- Snyder JE, Kulcsar KA, Schultz KL, Riley CP, Neary JT, Marr S, Jose J, Griffin DE, Kuhn RJ. Functional characterization of the alphavirus TF protein. J Virol. 2013 Aug;87(15):8511-23. doi: 10.1128/JVI.00449-13. Epub 2013 May 29. PubMed PMID: 23720714; PubMed Central PMCID: PMC3719798.
- Snyder JE, Berrios CJ, Edwards TJ, Jose J, Perera R, Kuhn RJ. Probing the early temporal and spatial interaction of the Sindbis virus capsid and E2 proteins with reverse genetics. J Virol. 2012 Nov;86(22):12372-83. doi: 10.1128/JVI.01220-12. Epub 2012 Sep 5. PubMed PMID: 22951842; PubMed Central PMCID: PMC3486501.
- Jose J, Przybyla L, Edwards TJ, Perera R, Burgner JW 2nd, Kuhn RJ. Interactions of the cytoplasmic domain of Sindbis virus E2 with nucleocapsid cores promote alphavirus budding. J Virol. 2012 Mar;86(5):2585-99. doi: 10.1128/JVI.05860-11. Epub 2011 Dec 21. PubMed PMID: 22190727; PubMed Central PMCID: PMC3302261.
- Tang J, Jose J, Chipman P, Zhang W, Kuhn RJ, Baker TS. Molecular links between the E2 envelope glycoprotein and nucleocapsid core in Sindbis virus. J Mol Biol. 2011 Dec 2;414(3):442-59. doi: 10.1016/j.jmb.2011.09.045. Epub 2011 Oct 4. PubMed PMID: 22001018; PubMed Central PMCID: PMC3407685.
- Snyder JE, Azizgolshani O, Wu B, He Y, Lee AC, Jose J, Suter DM, Knobler CM, Gelbart WM, Kuhn RJ. Rescue of infectious particles from preassembled alphavirus nucleocapsid cores. J Virol. 2011 Jun;85(12):5773-81. doi: 10.1128/JVI.00039-11. Epub 2011 Apr 6. PubMed PMID: 21471237; PubMed Central PMCID: PMC3126313.
- Gualtieri EJ, Guo F, Kissick DJ, Jose J, Kuhn RJ, Jiang W, Simpson GJ. Detection of membrane protein two-dimensional crystals in living cells. Biophys J. 2011 Jan 5;100(1):207-14. doi: 10.1016/j.bpj.2010.10.051. PubMed PMID: 21190673; PubMed Central PMCID: PMC3010839.
- Li L, Jose J, Xiang Y, Kuhn RJ, Rossmann MG. Structural changes of envelope proteins during alphavirus fusion. Nature. 2010 Dec 2;468(7324):705-8. doi: 10.1038/nature09546. PubMed PMID: 21124457; PubMed Central PMCID: PMC3057476.
- Jose J, Snyder JE, Kuhn RJ. A structural and functional perspective of alphavirus replication and assembly. Future Microbiol. 2009 Sep;4(7):837-56. doi: 10.2217/fmb.09.59. Review. PubMed PMID: 19722838; PubMed Central PMCID: PMC2762864.
- Gopal P, Pravin Kumar P, Sinilal B, Jose J, Kasin Yadunandam A, Usha R. Differential roles of C4 and betaC1 in mediating suppression of post-transcriptional gene silencing: evidence for transactivation by the C2 of Bhendi yellow vein mosaic virus, a monopartite begomovirus. Virus Res. 2007 Jan;123(1):9-18. doi: 10.1016/j.virusres.2006.07.014. Epub 2006 Sep 1. PubMed PMID: 16949698.
- Jose J, Usha R. Bhendi yellow vein mosaic disease in India is caused by association of a DNA Beta satellite with a begomovirus. Virology. 2003 Jan 20;305(2):310-7. doi: 10.1006/viro.2002.1768. PubMed PMID: 12573576.