Molecular Mechanism of PACT-dependent Innate Antiviral Response

Professor Jin, Dong-Yan   (Project Coordinator (PC))

Dr Yeung Man Lung   (Co-principal investigator)

Dr Chan Chi Ping   (Co-principal investigator)

Professor Sham Mai Har   (Co-principal investigator)

Dr Zhou Jie   (Co-principal investigator)

Professor Zheng Bojian   (Co-principal investigator)

Professor Yuen Kwok Yung   (Co-principal investigator)

Professor Au Shannon Wong Ngor   (Co-principal investigator)

36

2016-06-01

7555731

Molecular Mechanism of PACT-dependent Innate Antiviral Response

hepatitis B virus, influenza A virus, innate antiviral response, PACT, virus-host interaction

Virology,Infection/Parasitology

C7011-15R

Collaborative Research Fund (CRF) - Group Research Project

2015

Completed

1. We will use a combination of methods in protein biochemistry and molecular immunology to define the mechanism for PACT activation of MDA5 in vitro and in vivo. Particularly, we will delineate the molecular basis of PACT-induced oligomerization of MDA5. The antiviral activity of PACT against encephalomyocarditis virus (EMCV) sensed by MDA5 will also be documented. 2. We will determine the dual antiviral function of PACT in IAV infection. The interaction of PACT with viral polymerase subunits PA, PB1 and PB2 as well as their mutual antagonism will be characterized. We will elucidate the mechanism by which PA, PB1 and PB2 inhibit PACT activation of innate antiviral response. We will also shed light on the roles of PACT in viral RNA sensing and in the inhibition of viral replication. 3. We will determine the dual antiviral function of PACT in the context of HBV infection. The requirement of PACT for innate sensing of the ε element on pgRNA of HBV and the induction of type III IFNs will be established. The molecular determinants on the ε element required for the activation of PACT will be delineated. The mechanism by which PACT inhibits the function of the 􀀀 element in HBV replication will be elucidated.