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 Group explores the role of the HEV ORF3 protein in viral pathogenesis. Our earlier work indicated a role for this protein in cell survival and proliferation through modulation of the extracellularly regulated kinase (a MAP kinase) pathway. Recent results show that the ORF3 protein protects cells from mitochondrial depolarization and death. It localizes to early and recycling endosomes, intersects the endocytic machinery and delays the degradation of activated growth factor receptors, a block in nuclear translocation of STAT3 and an attenuated acute phase response. Thus, in addition to a pro-survival and proliferative function, the ORF3 protein may also protect HEV from innate host immunity. Recent results also show an effect of this protein on cellular energy homeostasis. Our extended studies have shown the ORF3 protein of HEV to be an important viral regulatory protein (see Figure). Two other lines of investigation are being pursued on HEV. The binding and endocytosis of capsid (ORF2) protein virus-like particles to cultured cells is being studied as a model to understand virus attachment and entry. The genomic, proteomic and immunological profiling of hepatitis E patients is 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 have also started using genomic (microarrays) and metabolomic (NMR) tools towards a comprehensive biomarker discovery programme.
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. Current work is aimed at characterizing the Nef-CD80/CD86 interactions and structural details of this complex. We recently found novel cellular binding partners for the Vpu protein. One of these, CD74, is being studied for its role in Vpu-mediated modulation of MHCII presentation and signaling. We are developing a murine model of HIV infection to enable in vivo studies on the roles of these viral proteins. Indians are infected with phylogenetically distinct strains of HIV and hepatitis C virus (HCV). In a new project we have started studying immune responses and the dynamics of viral receptors/coreceptors in HCV-HIV co-infected persons. A biomarker discovery programme based on genomic, proteomic and metabolomic analyses is being initiated in various groups of HIV-infected persons.
Pathogen dectection and discovery
We have initiating a new programme to use high-throughput multiplex technologies to map the pathogen ecology in select clinical situations. In the initial phase, these include respiratory infections and encephalitis. The short-term goal is to establish a staged strategy for efficient surveillance and differential diagnosis of infectious diseases, and pathogen discovery. In the longer term, we aim to build a laboratory infrastructure for rapid and multiplex diagnostics, and to apply these for the discovery of new infectious etiologies.

Recent Publications

Moin, S.M., Chandra, V., Arya, R., Jameel, S. 2009. The hepatitis E virus ORF3 protein stabilizes HIF-1a and enhances HIF-1 mediated transcriptional activity through p300/CBP. Cell. Microbiol. 11, 1409-1421

Chandra, V., Kar-Roy, A., Kumari, S., Mayor, S., Jameel, S. 2008. The HEV ORF3 protein modulates EGFR trafficking, STAT3 translocation and the acute phase response. J. Virol. 82, 7100-7110

Padhan, K., Minakshi, R., Towheed, M.A.B., Jameel, S. 2008. The SARS coronavirus 3a protein activates the mitochondrial death pathway through p38 MAP kinase activation. J. Gen. Virol. 89, 1960-1969

Dubey, S., Khalid, M., Wesley, C., Khan, S.A., Wanchu, A., Jameel, S. 2008. Down regulation of CCR5 on activated CD4 T cells in HIV-infected Indians. J. Clin. Virol. 43, 25-31

Hussain, A., Wesley, C., Khalid, M., Chaudhry, A., Jameel, S. 2008. The HIV-1 Vpu protein interacts with CD74 and modulates major histocompatibility complex II presentation. J. Virol. 82, 893-902

Moin, S.M., Panteva, M., Jameel, S. 2007. The hepatitis E virus (HEV) ORF3 protein protects cells from mitochondrial depolarization and death. J. Biol. Chem. 282, 21124-21133