David A. Jans, Leon Caly, Monika Bajonek, Jason Oï¿½Donnell, Weilin Wu, John Mills, Ralph A. Tripp and Reena Ghildyal
Scientific Tracks Abstracts: J Antivir Antiretrovir
Respiratory syncytial virus (RSV) is the major respiratory pathogen of infants and children worldwide, with no effective treatment or vaccine available. The RSV matrix protein (M) is critical to the virus, playing a key cytoplasmic role in virus assembly late in infection (1,2). Intriguingly, however, it is localized in the nucleus of infected cells early in infection through the action of the importin (IMP) �?²1 nuclear transporter; prevention of M-IMP�?²1 interaction in mutant RSV reduces virus production over 20-fold, indicating that M nuclear localization is critical to the RSV life cycle (3). The role of M in the nucleus appears to be to inhibit host cell transcription, thereby dampening the host anti-viral response, but the mechanism thereof has not been defined. We set out to address this question using a 3-pronged screening approach to look for nuclear targets of M action, through yeast 2-hybrid screening and proteomic approaches, and subsequent assessment the importance of the cellular factor to RSV infection by siRNA knockdown. A range of potential targets of M were identified, and are beginning to be validated, our initial results indicating the power of our 3-pronged screening approaches. (1) J. Virol. 82, 8863-8870 (2008); (2) Infectious Disorders-Drug Targets 12, 103-109 (2012); (3) J. Virol. 83, 5353-5362 (2009).
Prof. Jans completed his Ph.D at the age of 25 years at the Australian National University (Canberra) and postdoctoral studies at the Friedrich Miescher Institut (Basel, Switzerland) and Max Planck Institut fuer Biophysik (Frankfurt am Main, Germany). He is presently an NHMRC Senior Principal Research Fellow (SPRF1) and Head of the Nuclear Signalling Lab. at Monash University (Melbourne, Australia). His research over the last 16 years has focused on the regulation of transport into and out of the eukaryotic cell nucleus, and how this relates to viral disease, cancer and development, and how it may be exploited for drug delivery. He has >240 peer-reviewed publications in eminent journals (> 7000 citations; H-factor of 54), has served as committee member of the International Photodynamic Association (2005-2011), and currently serves as an editorial board member of Biochemical Journal (since 2006), Biochem Biophys Acta Mol Cell Res (since 2010) and Antiviral Res (since 2012).