Abstract
BackgroundMeasles virus nucleoprotein (N) encapsidates the viral RNA, protects it from endonucleases and forms a virus specific template for transcription and replication. It is the most abundant protein during viral infection. Its C-terminal domain is intrinsically disordered imparting it the flexibility to interact with several cellular and viral partners.Principal FindingsIn this study, we demonstrate that expression of N within mammalian cells resulted in morphological transitions, nuclear condensation, DNA fragmentation and activation of Caspase 3 eventuating into apoptosis. The rapid generation of intracellular reactive oxygen species (ROS) was involved in the mechanism of cell death. Addition of ascorbic acid (AA) or inhibitor of caspase-3 in the extracellular medium partially reversed N induced apoptosis. We also studied the protein profile of cells expressing N protein. MS analysis revealed the differential expression of 25 proteins out of which 11 proteins were up regulated while 14 show signs of down regulation upon N expression. 2DE results were validated by real time and semi quantitative RT-PCR analysis.ConclusionThese results show the pro-apoptotic effects of N indicating its possible development as an apoptogenic tool. Our 2DE results present prima facie evidence that the MV nucleoprotein interacts with or causes differential expression of a wide range of cellular factors. At this stage it is not clear as to what the adaptive response of the host cell is and what reflects a strategic modulation exerted by the virus.
Highlights
Measles virus nucleoprotein (N) packages the nonsegmented, negative-sense, single-stranded RNA genome of measles virus to form the helical nucleocapsid [1,2,3]
We identified proteins involved in apoptosis and reactive oxygen species (ROS) management, but we identified a number of novel alterations to the cellular proteome
While the results presented here are expected to offer some clues to further study the viral infection mechanisms, we see a new trigger to induce cell death in the measles virus nucleoprotein which is amenable to re-engineering as a targeted molecule
Summary
Measles virus nucleoprotein (N) packages the nonsegmented, negative-sense, single-stranded RNA genome of measles virus to form the helical nucleocapsid [1,2,3]. There are signs of reactive oxygen species (ROS) building up in cells expressing N. Pretreatment of ascorbic acid (AA) partially counteracts ROS generation and apoptosis. We show that N triggers apoptosis through generation of ROS and caspase-3 activation. Measles virus nucleoprotein (N) encapsidates the viral RNA, protects it from endonucleases and forms a virus specific template for transcription and replication. It is the most abundant protein during viral infection. Its C-terminal domain is intrinsically disordered imparting it the flexibility to interact with several cellular and viral partners
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