Research Groups
Mammalian Biology: Virology
Research Interests and Description
Research Interests
HEV, HIV, host-virus interactions, biomarkers, pathogen detection and discovery.
Description of Research
Hepatitis E virus
The Hepatitis E virus (HEV) is endemic to large parts of the world with about 2 billion people at risk of infection. Our Group has worked extensively on the biology and pathogenesis of HEV. Our earlier work has indicated a role for the ORF3 protein in cell survival and proliferation. We have also shown that the ORF3 protein localizes to early and recycling endosomes and have delineated the mechanistic details of its effects on growth factor receptors and the acute phase response. Most recently, through microarray analyses, we have studied the global effects of this protein on liver cells and find large-scale regulation of genes driven by the transcription factor HNF4. Thus, our extended studies have shown the ORF3 protein of HEV to be an important viral regulatory protein. We have also studied the interaction of HEV and its capsid protein with liver cells. This has led to the discovery of heparan sulfate proteoglycans (HSPGs) as attachment factors for HEV. We are now pursuing the identification and characterization of a cellular receptor for HEV. The genomic, proteomic and immunological profiling of hepatitis E patients is also being pursued to understand pathogenesis and to discover useful biomarkers of disease progression. Using proteomic tools, we have discovered changes in the plasma and urine proteomes of hepatitis patients and have validated these as potential biomarkers. We are also using genomic (microarrays) and metabolomic (NMR) tools towards a comprehensive biomarker discovery programme. These studies have also allowed us to build a comprehensive model of HEV pathogenesis and its detrimental effects on pregnant women.
Human immunodeficiency virus
We study the HIV-1 accessory proteins Nef and Vpu for their roles in pathogenesis. The Nef protein was found to down modulate the surface levels of B7 family costimulatory molecules (CD80 and CD86) on antigen-presenting cells through a novel endocytic pathway. We are now using cell culture models and clinical samples from patients to understand the effects of HIV infection and Nef in particular, on host gene expression and on small regulatory RNAs (e.g. miRNAs). Our profiling studies show large-scale deregulation and export of cellular miRNAs in Nef-expressing monocytic cells. The mechanisms for these are being studied. We have found novel cellular binding partners for the HIV-1 Vpu protein and, in particular, CD74 is being studied for its role in Vpu-mediated modulation of MHCII presentation and signaling. Indians are infected with phylogenetically distinct strains of HIV and hepatitis C virus (HCV). Co-infection with these two viruses results in faster progression to fibrosis, an early event in liver damage. We are using stellate cell culture models of fibrosis to better understand this process and identify critical factors.
Pathogen dectection and discovery
We have used high-throughput multiplex technologies to map the pathogen ecology in selected clinical situations. In the initial phase, these have included studies on the ecology of respiratory infections and the first evidence of a new respiratory virus infection in Indian patients. The long-term aim is to build a laboratory infrastructure for rapid and multiplex diagnostics towards the discovery of new infectious etiologies.
Recent Publications
Ahmad, I., Holla, R.P., Jameel, S. 2011. Molecular virology of hepatitis E virus. Virus Res 161, 47-58 PubMed link
Chandra, V., Holla, P., Ghosh, D., Chakrabarti, D., Padigaru, M., Jameel, S. 2011. The Hepatitis E Virus ORF3 Protein Regulates the Expression of Liver-Specific Genes by Modulating Localization of Hepatocyte Nuclear Factor 4. PLoS One 6, e22412 PubMed link
Munshi, S.U., Taneja, S., Bhavesh, N.S., Shastri, J., Aggarwal, R., Jameel, S. 2011. Metabonomic analysis of hepatitis E patients shows deregulated metabolic cycles and abnormalities in amino acid metabolism. J Viral Hepat 18, e591-602 PubMed link
Taneja, S., Ahmad, I., Sen, S., Kumar, S., Arora, R., Gupta, V.K., Aggarwal, R., Narayanasamy, K., Reddy, V.S., Jameel, S. 2011. Plasma peptidome profiling of acute hepatitis E patients by MALDI-TOF/TOF. Proteome Sci 9, 5 PubMed link
Chandra, V., Kalia, M., Hajela, K., Jameel, S. 2010. 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. J Virol 84, 3857-3867 PubMed link
Kalia, M., Chandra, V., Rahman, S.A., Sehgal, D., Jameel, S. 2009. Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. J Virol 83,12714-12724 PubMed link
