Investigating Pteropus Orthoreovirus Antagonism of Interferon Regulatory Factor 9 Siew Kit Ng1, Alvin Paul1, Kenny Gah Leong Voon2 1Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia; 2School of Medicine, International Medical University, Kuala Lumpur, Malaysia
Interferon Regulatory Factor 9 (IRF9) was first identified as the gamma-component of Interferon Stimulated Gene Factor 3 (ISGF3) complex responsible in massive upregulation of interferon-stimulated genes (ISGs) following viral infection. These ISGs will contribute towards highly effective antiviral cellular state in the infected and neighbouring cells. Activation of ISGF3 is tightly regulated through the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway. As such, the JAK-STAT signalling pathway is targeted by viruses to mitigate host antiviral response. For example, the µ2 protein from mammalian orthoreovirus is known to inhibit IRF9 function through promoting nuclear accumulation of IRF9. Here we aim to first prove, and then understand the mechanistic details regarding IRF9 antagonism by the homologous µA protein from Pteropus Orthoreovirus (PRV). The initial stage involves monitoring the localization of IRF9 following µA protein overexpression or PRV infection in NP69 human nasopharygeal cells. Biochemical and structural analysis will then be carried out to elucidate the interaction between IRF9 and µA protein. Comparative studies using fruit bat cells (PaKi and PaLu) may provide further insight on the differences between fruit bats (reservoir) and humans (infected mammalian host) in their innate response to PRV.