It has become apparent that the microbes outnumber human cells within an individual. At least virus-like particles are estimated to be present per gram of human feces, representing the gut virome. Evidences are emerging to support that the gut virome has medical relevance as it plays an important role in human health and physiology.

Earlier studies have indicated a need to examine the diversity of gut virome in additional distinct populations. One of our aims is to create an in-depth inventory of viruses present in the distal gut of Indian population. It is of interest for devising rational approaches to develop therapeutics as well as identify biomarkers for conditions such as inflammatory gut conditions, metabolic syndromes, colorectal cancer and diseases of the central nervous system that are associated with gut microbiome dysbiosis. In addition, our interest is to look for novel viruses and viral proteins for bio-prospecting. Our approaches mainly involve shotgun sequencing of the nucleic acids purified from fecal virus-like particles (VLPs) and total fecal DNA followed by bioinformatics analyses.

To be able to fully harness the therapeutic, diagnostic and biotechnological potential of the human gut virome, there is also a need to reveal and characterize the functionality encoded by the gut viruses. Our other aim is to map the functional landscape of the gut virome and understand the molecular mechanisms by which the newly identified viruses/phages found in the human gut interact with the host. We are also investigating the host interaction of the pathogenic human viruses, SARS-coronavirus and chikungunya virus. It involves bioinformatics and experimental approaches.

• Himani Sharma
  Senior Research Fellow
  himani.sharma@rcb.res.in

1. Bhardwaj K (2013). How prepared are we to control severe acute respiratory syndrome in future. American Journal of Virology. 2: 8-19. (An invited review article). ( corresponding author)
2. Bhardwaj K, Liu P, Leibowitz JL, Kao CC (2012) The Coronavirus endoribonuclease Nsp15 interacts with Retinoblastoma tumor suppressor protein. Journal of Virology 86(8):4294. ( corresponding author)
3. Lai Y, Adhikarakunnathu S, Bhardwaj K, Ranjith-Kumar CT, Wen Y, Jordan J, Wu L, Dragnea B, San Mateo L and Kao CC (2011). LL37 and cationic peptides enhance TLR3 signaling by viral double-stranded RNAs. PLoS ONE 6(10):e26632.
4. Lai Y, Yi G, Chen A, Bhardwaj K, Valverde RA, Zlotnick A, Mukhopadhyay S, Ranjith-Kumar CT, and Kao CC (2011) Viral double-strand RNA-binding proteins can enhance innate immune signaling by toll-like receptor 3. PLoS ONE 6(10):e25837.
5. Ranjith-Kumar CT, Wen Y, Baxter N, Bhardwaj K and Kao CC (2011). A cell-based assay for RNA synthesis by the HCV polymerase reveals new insights on mechanism of polymerase inhibitors and modulation by NS5A. PLoS ONE 6(7): e22575. doi:10.1371/journal.pone.0022575.
6. Ortiz-Alcantara J, Bhardwaj K, Palaninathan S, Frieman M, Baric RS, Kqo CC (2010). Small molecule inhibitors of SARS-CoV Nsp15 endoribonuclease, mechanism of action and insight into coronavirus infection. Virus Adaptation and Treatment 2: 125-133.
7. Mao C, Bhardwaj K, Sharkady SM, Fish RI, Driscoll T, Wower J, Zwieb C, Sobral BW, Williams KP (2009).Variations on the tmRNA gene. RNA Biology 6(4) 355-361 Cover illustration. ( equal contributors).
8. Ranjith-Kumar CT, Murali A, Dong W, Srisathiyanarayanan D, Vaughan R, Alcantara JMO, Bhardwaj K, Li X, Li P, Kao CC (2009). Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor. Journal of Biological Chemistry 284(2):1155-1165.
9. Murali A, Li X, Ranjith-Kumar CT, Bhardwaj K, Holzenburg A, Li P, Kao CC (2008). Structure and function of LGP2, a DExD/H helicase that regulates the innate immunity response. Journal of Biological Chemistry 283(23):15825-15833.
10. Bhardwaj K, Palaninathan S, Alcantara JMO, Yi L, Guarino L, Sacchettini, JC, Kao CC (2008). Structural and Functional Analyses of the SARS Coronavirus Endoribonuclease Nsp15. Journal of Biological Chemistry 283(6):3655-3664.
11. Kang H, Bhardwaj K, Yi L, Palaninathan S, Sacchettini J, Guarino L, Kao C, Leibowitz, JL (2007). Biochemical and Genetic Analyses of the Mouse Hepatitis Virus Nsp15 Endoribonuclease. Journal of Virology 81(24):13587-13597 ( equal contributors).
12. Ranjith-Kumar CT, Miller W, Xiong J, Russell WK, Lamb R, Santos J, Duffy KE, Cleveland L, Park M, Bhardwaj K, Wu Z, Russell DH, Sarisky RT, Mbow ML, Kao CC (2007). Biochemical and functional analyses of the human Toll-like receptor 3 ectodomain. Journal of Biological Chemistry 282(10):7668-7678.
13. Bhardwaj K, Sun J, Holzenburg A, Guarino LA, Kao CC (2006). RNA recognition and cleavage by the SARS Coronavirus endoribonuclease. Journal of Molecular Biology 361(2):243-256.
14. Guarino LA, Bhardwaj K, Dong W, Sun J, Holzenburg A, and Kao C (2005). Mutational analysis of the SARS Virus Nsp15 endoribonuclease: Identification of residues affecting hexamer formation. Journal of Molecular Biology 353(5):1106-1117.
15.  Jacob Y, Sharkady SM, Bhardwaj K, Sanda A and Williams KP (2004). Function of the SmpB tail in tmRNA translation revealed by a Nucleus-encoded form. Journal of Biological Chemistry 280(7): 5503-5509.
16. Bhardwaj K, Guarino LA, and Kao CC (2004). The SARS coronavirus Nsp15 protein is an endoribonuclease that prefers manganese as cofactor. Journal of Virology 78(22): 12218-12224.
17. Lata S, Bhardwaj K, and Rajasekharan R (2003). A single-step procedure for the synthesis of photoreactive and radioactive glycerolipids. Analytical Biochemistry 313(1):155-9.
18. Bhardwaj K, Raju A, and Rajasekharan R (2001). Identification, purification, and characterization of a thermally stable lipase from rice bran. A new member of the (phospho) lipase family. Plant Physiology 127(4):1728-38.

Patents:

1. Rajasekharan, R. and Bhardwaj, K. (2002). Process of isolation and utilization of rice bran lipase - PCT International Publication No. WO 02/101033.
2. Kanchan Bhardwaj and C. Cheng Kao (2012). A Cell-Based Assay for the activity of the Mitochondrial RNA Polymerase. US Provisional Patent Application No. 61/608,202.