Microbiology, Molecular Genetics and Immunology
Ph.D., Saha Institute of Nuclear Physics, Department of Atomic Energy, Kolkota, India, 2003
Postdoctoral Fellow, University of New Mexico, Albuquerque, NM, USA
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Negative stranded RNA viruses cause serious human illness and there is a growing concern over the emergence of virulent pathogenic strains such as swine flu and avian influenza. During virus replication negative stranded viral genome is copied into plus sense viral mRNA by viral RNA dependent RNA polymerase (RdRp) and the resulting viral mRNAs are translated by host cell translation apparatus. My laboratory focuses on transcription and translation initiation of viral mRNA from negative stranded RNA viruses with an emphasis on hantavirues. Hantaviruses are emerging viruses and category A pathogens that cause hantavirus cardiopulmonary syndrome with a motility of fifty percent. They have a tripartite negative sense RNA genome and comprise a genus in the Bunyaviridae family. Current research projects are:
Transcription of hantaviral mRNA: The minus stranded and ambisense segmented RNA viruses initiate the viral mRNA synthesis by the process of "cap-snatching". During this process viruses cleave the cellular capped mRNAs from the 5' terminus and generate capped RNA oligoes that are used as primers by viral RdRp during transcription initiation. However, during routine mRNA turnover, the 5' caps of cellular mRNAs are cleaved by decapping enzymes DCP1/DCP2, followed by 5' to 3' degradation by exonuclease XRN1. Viruses have to effectively compete with cellular decapping machinery to preserve the caps for the successful initiation of viral mRNA synthesis. We are studying the viral strategies that protect the 5' caps of cellular mRNAs from the attack of decapping machinery. We are also interested to identify and characterize the endonuclease required for the generation of capped RNA primer during cap snatching.
Translation initiation of hantaviral mRNA: The majority of mRNA translation within eukaryotic cells is dependent on the m7G cap. Although cap-dependent translation provides several advantages to the host cell, it also presents liabilities that are effectively exploited by the viruses. Modulation of host cell translation machinery is a selfish viral strategy to favor the translation of viral mRNAs despite attempts of the host cell to shut down translation, and despite the competition of host cell mRNA for the same translation apparatus. We have recently found that hantaviruses nucleocapsid protein functions in trans to engage small ribosomal subunit at mRNA 5' cap, functionally replacing the cellular eIF4F cap binding complex. We are currently studying how N mediated translation initiation benefits virus replication in host cells, with an emphasis to delineate whether N medicated translation strategy is a viral counter measure against host cell antiviral response.
Mohammad Ayoub Mir, Ph.D.
Office: 4001 Hixon
Lab: 4022 Orr Major
Lab: (913) 588-5579