Our laboratory is focused on understanding the fundamental molecular mechanisms of gene expression of nonsegmented negative strand (NNS) RNA viruses. NNS RNA viruses include many important human pathogens, such as rabies, human parainfluenza, respiratory syncytial, measles, and Ebola; however, at present there are no effective drugs against these viruses.
To investigate the common mechanisms of mRNA biogenesis mediated by multifunctional large (L) proteins of NNS RNA viruses, we have established in vitro mRNA synthesis and processing assay systems using vesicular stomatitis virus (VSV), a prototype of NNS RNA viruses, as a model. Using these systems, we have revealed that the mechanism of mRNA capping, one of the major mRNA processing events, catalyzed by the VSV L protein, is fundamentally different from that of eukaryotic host cells. Furthermore, we have discovered that unique amino acid sequence motifs required for the mRNA capping activity of the VSV L protein are highly conserved among NNS RNA viral L proteins and are essential for VSV growth. These findings suggest that the NNS RNA viral mRNA capping enzyme is a potential drug target. Our current interests are to define the structure and function of NNS RNA viral L proteins and to find small molecule inhibitors against them.
Ogino T. (2013) In vitro capping and transcription of rhabdoviruses. Methods 59(2):188-198. [PubMed]
Fensterl V, Wetzel JL, Ramachandran S, Ogino T, Stohlman SA, Bergmann CC, Diamond MS, Virgin HW, Sen GC. (2012) Interferon-induced Ifit2/ISG54 protects mice from lethal VSV neuropathogenesis. PLoS Pathog. 8(5):e1002712. [PubMed]
Ogino T, Banerjee AK. (2011) An unconventional pathway of mRNA cap formation by vesiculoviruses. Virus Res. 162(1-2):100-109. Review. [PubMed]
Ogino T, Yadav SP, Banerjee AK. (2010) Histidine-mediated RNA transfer to GDP for unique mRNA capping by vesicular stomatitis virus RNA polymerase. Proc Natl Acad Sci U S A. 107(8):3463-3468. [PubMed]
Ogino T, Banerjee AK. (2010) The HR motif in the RNA-dependent RNA polymerase L protein of Chandipura virus is required for unconventional mRNA-capping activity. J Gen Virol. 91(Pt 5):1311-1314. [PubMed]
Ogino T, Banerjee AK. (2008) Formation of guanosine(5')tetraphospho(5')adenosine cap structure by an unconventional mRNA capping enzyme of vesicular stomatitis virus. J Virol. 82(15):7729-7734. [PubMed]
Ogino T, Banerjee AK. (2007) Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of vesicular stomatitis virus. Mol Cell. 25(1):85-97. [PubMed]