Research Groups

Mammalian Biology: Virology

Research Interests and Description

Staff Research Scientist: Sunil Kumar Lal

Research Interests

Host-virus relationships at the protein-protein interaction level for respiratory viruses, avian influenza and SARS.

Description of Research

SARS coronavirus
Since the outbreak of the SARS epidemic in South-East Asia, we have been focusing on the molecular biology of the SARS-CoV. To date we have shown that the N protein of the SARS virus is significantly different from other Coronavirus N proteins by its ability to self-associate, induce apoptosis and actin reorganization in mammalian cells under stress, get phosphorylated by the cyclin-CDK complex and deregulate the cell-cycle. The Group believes these findings will have long standing implications on viral pathogenesis, which results in the death of infected humans. The SARS-CoV accessory protein 3a has been shown to interact with the spike, envelope and membrane glycoprotein and has recently been established to be a structural component of capsid. The Group initiated studies to check its RNA binding activity and showed that the 3a protein was capable of binding specifically to the 5' untranslated region (5'UTR) of the SARS virus genomic RNA. Further, we mapped the interaction domain of the 3a protein responsible for this RNA-protein interaction using a series of deletion mutants and defined it to the central 75 amino acid region. This RNA binding motif of 3a does not share homology with any other known RNA binding protein and may have an important role in viral capsid assembly and pathogenesis.
Influenza A (H5N1/H1N1) virus
Keeping in mind the severity of the “bird-flu” and “swine-flu” outbreaks and the potential pandemic threats posed by the influenza virus, the Group has recently initiated an active research program on this virus. We have recently discovered that the nucleocapsid protein (NP) of H5N1 interacts with heat shock protein (hsp) 40. Further, the levels of pPKR and phospho-eIF2alpha (the downstream target of PKR) were found to be down regulated in NP transfected cells. We subsequently used siRNA against NP to confirm our hypothesis and found that in the presence of siRNA, the levels of peIF2alpha returned to normal. We are currently studying this lead in detail and have discovered similar new host-viral interactions and virus evolution across different viral isolates.

Recent Publications

Ratra, R., Kar-Roy, A., Lal, S. K. 2009. The ORF3 protein of Hepatitis E virus interacts with the b beta chain of fibrinogen resulting in decreased fibrinogen secretion from HuH-7 cells. J. Gen. Virol. 90, 1359-1370

Ratra, R., Kar-Roy, A., Lal, S. K. 2008. The ORF3 Protein of Hepatitis E Virus Interacts with hemopexin by means of its 26 Amino Acid N-terminal hydrophobic domain II.Biochemistry 47, 1957-1969

Lal, S.K., ed. 2007. The Biology of Emerging Virusus. Blackwell Publishers, USA.

Surjit, M., Jameel, S., Lal, S.K. 2007. Cytoplasmic localization of the ORF2 protein of Hepatitis E Virus is dependent on its ability to undergo retro-translocation from the endoplasmic reticulum. J. Virol. 81, 3339-3345

Lal, S.K., ed. 2006. Emerging Viral Infections of Southeast Asia. Karger, Switzerland.

GenBank Submissions

Accession No: EU185058; EU185057; EU185056; EU189941; EU180218; EU180217; EU180216; EU180215; EU170436; EU170435; EU170434; EU085422; EU085421; EU085420; DQ862475; DQ862474; DQ862473; DQ862472; AJ867074; AJ867075; AJ867076; AM040046; AM040045