C. Cheng Kao
Professor
Department of Biochemistry and Biophysics
Education
B.Sc. - University of Michigan (1984)
Ph.D. - Michigan State University (1988)
Postdoc. - UCLA and University of Wisconsin (1988-90)
Research Interests
We study the replication mechanism of (+)strand RNA viruses including brome
mosaic virus and hepatitis C virus. Our primarily biochemical studies address
both basic steps in RNA synthesis and the means to inhibit viral RNA synthesis.
Brome mosaic virus (BMV) is a small plus-strand RNA virus that infects barley
and wheat. BMV is a good model system for studies of RNA replication because
it has a well-defined genome that encodes only four known proteins; its
replication can be studied with convenient in vitroassays and in the genetically
amenable yeast, Saccharomyces cerevisiae. Finally, since almost all characterized
plant viruses and many animal viruses have genomes composed of RNA, what
is learned about BMV will be of use in understanding other less easily studied
viruses. Our studies of BMV RNA replication are focused on two main areas:
1) elucidation of the structure and activities of the replicase enzyme and
2) dissecting the steps in RNA synthesis by a viral replicase.
The genome of Hepatitis C virus (HCV) was recently cloned, permitting a
detailed analysis of the mechanism of HCV RNA synthesis. Using the protocols
established for BMV RNA replication, we have elucidated how the HCV polymerase
recognizes HCV RNAs and initiates RNA synthesis. We are also designing protocols
that will improve detection of RNA products synthesized from RNA templates.
This work has relevance to anti-HCV drug design.
Representative Publications
Chen C, Daniel MC, Quinkert ZT, De M, Stein B, Bowman VD, Chipman PR, Rotello
VM, Kao CC, Dragnea B. 2006.Nanoparticle-templated assembly of
viral protein cages. Nano Lett.6:611-5.
Chen C, Kwak ES, Stein B, Kao CC, Dragnea B. 2005. Packaging of
gold particles in viral capsids. J Nanosci Nanotechnol, 5:2029-33.
Ranjith-Kumar CT, Kao CC. 2006. Recombinant viral RdRps can initiate
RNA synthesis from circular templates. RNA. 12:303-12.
Kim YC, Russell WK, Ranjith-Kumar CT, Thomson M, Russell DH, Kao CC.
2005.Functional analysis of RNA binding by the hepatitis C virus RNA-dependent
RNA polymerase. J Biol Chem. 280:38011-9.
Kao CC, Green S, Stein B, Golden SS. 2005. Diel infection of a
cyanobacterium by a contractile bacteriophage. Appl Environ Microbiol. 71:4276-9.
Bhardwaj K, Guarino L, Kao CC. 2004. The severe acute respiratory
syndrome coronavirus Nsp15 protein is an endoribonuclease that prefers manganese
as a cofactor. J Virol. 78:12218-24.
Ranjith-Kumar CT, Sarisky RT, Gutshall L, Thomson M, Kao CC. 2004.
De novo initiation pocket mutations have multiple effects on hepatitis C
virus RNA-dependent RNA polymerase activities. J Virol. 78:12207-17.
Sivakumaran K, Choi SK, Hema M, Kao CC. 2004.Requirements for brome
mosaic virus subgenomic RNA synthesis in vivo and replicase-core promoter
interactions in vitro. J Virol. 78:6091-101.
Hema M, Kao CC. 2004.Template sequence near the initiation nucleotide
can modulate brome mosaic virus RNA accumulation in plant protoplasts. J
Virol.78:1169-80.
Ranjith-Kumar CT, Gutshall L, Sarisky RT, Kao CC. 2003. Multiple
interactions within the hepatitis C virus RNA polymerase repress primer-dependent
RNA synthesis. J Mol Biol. 330:675-85.
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