Study of global gene expression and immune responses induced by infection with NS1 deleted (DelNS1) influenza viruses

Professor Chen, Honglin   (Principal Investigator (PI))

36

2020-01-01

2022-12-31

892882

Study of global gene expression and immune responses induced by infection with NS1 deleted (DelNS1) influenza viruses

immunity, infection, Influenza virus, NS1, Vaccine

VirologyMicrobiology

Biology and Medicine (M)

17107019

General Research Fund (GRF)

2019

Completed

1 To characterize the molecular basis of the replication of DelNS1 viruses derived from influenza A (H5N1, 2009 H1N1 and 2013 H7N9 backbone) and influenza B strains. We found that these strains require different adaptive mutations to those previously identified in DelNS1 WSN and PR8 strains in order to support virus replication in the absence of the NS1 gene. Characterization of the molecular basis of how these adaptive mutations facilitate replication of these strains will be important for understanding the role of NS1 in influenza viruses with different genetic backgrounds. 2 Characterization of genome wide transcriptional responses in cells infected with DelNS1 and corresponding wild type viruses. This part of the study will provide a comprehensive analysis of host gene expression in response to influenza viruses of different pathogenic backgrounds, with and without expression of the NS1 protein, using RNA-seq technology. The specific focus will be on modulation of gene expression by NS1 through epigenetic mechanisms. 3 To characterize differential immune responses in mice infected with DelNS1 or wild type viruses. A comprehensive profile of the effects of the presence or absence of the NS1 protein on immune responses related to induction of adaptive immunity during primary infection will be compiled. The study will be focused on mechanisms related to immune responses leading to cross protective immunity induced by DelNS1 live attenuated viruses.