Characterization of low pathogenic avian influenza viruses subtype H5 isolated in Singapore and RNA interference as an antiviral strategy.

Low pathogenic avian influenza viruses (LPAIVs) have the potential to mutate into high pathogenic viruses, and transmission from avian to human host has been documented. We have characterized LPAIVs H5 subtype isolated in Singapore. Molecular sequence analyses revealed that the LPAIVs contained mainly avian signatures and no virulence-associated signatures. We examined the replication and growth characteristics of the LPAIVs in avian, canine and human cells, as well as in a mouse model of infection. Host responses to LPAIV infection were profiled and compared using microarrays and we found that the host gene expression was unique to each virus in each cell line, with the strongest antiviral response to the LPAIVs observed in human cells. Finally, we explored RNA interference as an anti-influenza strategy and developed several cell-based assays to rapidly evaluate custom-designed short-interfering (si)RNAs.Doctor of Philosophy (SBS