Our research focuses on the structure and mechanism of viral replication
and infection machinery using X-ray crystallography and cryo-electron
microscopy. High-resolution X-ray crystal structures of individual
component proteins can be fitted into lower resolution cryo-EM density
maps to generate pseudo-atomic structure of large macromolecular
Viral Genome Replication
Replication of the viral genome is the primary goal of any viral infection, and thus obtaining structural information on the flavivirus replicase complex is an important step in understanding the virus replication mechanism and in developing antiviral therapeutics. Many RNA viruses have the RNA capping machinery functionally and physically linked to the replication machinery as multi-domain and larger multi-protein complexes. We are currently investigating such replicase interactions in Flaviviridae.
Mammalian cells respond to viral infection by inducing an innate immune
response involving interferon α/β that mediates cellular antiviral
defenses. Viruses, in turn, have evolved mechanisms to counter the
host's innate immune response by inhibiting the interferon response.
We are studying how pestivirus Npro suppresses the transcriptional activation of the interferon-α/β genes.
Virus structure and assembly
Despite the significant impact of flavivirus infection such as Japanese encephalitis, dengue, yellow fever, and West Nile, no antiviral therapies are available for treatment and existing flavivirus vaccines are of limited utility. We use cryo-electron microscopy to study the structures of viruses and viral vaccine candidates to help develop vaccines and antiviral agents.