Biochemistry & Biophysics

C. Cheng Kao

kao Professor of Biochemistry and Biophysics

Phone: (979) 458-2235
Email:ckao@tamu.edu
B.Sc. University of Michigan (1984)
Ph.D. Michigan State University (1988)
Postdoc. UCLA and University of Wisconsin (1988-90)

Joined Texas A&M faculty in 2003

RNA Structure and Function / Mechanism of Virus RNA Replication
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.

Recent Publications
  1. Yi G, Vaughan RC, Yarbrough I, Dharmaiah S & Kao CC (2009) RNA binding by the brome mosaic virus capsid protein and the regulation of viral RNA accumulation. J Mol Biol 391: 314-26
  2. Yi G, Letteney E, Kim CH & Kao CC (2009) Brome mosaic virus capsid protein regulates accumulation of viral replication proteins by binding to the replicase assembly RNA element. RNA 15: 615-26
  3. Aniagyei SE, Kennedy CJ, Stein B, Willits DA, Douglas T, Young MJ, De M, Rotello VM, Srisathiyanarayanan D, Kao CC & Dragnea B (2009) Synergistic effects of mutations and nanoparticle templating in the self-assembly of cowpea chlorotic mottle virus capsids. Nano Lett 9: 393-8
  4. Ranjith-Kumar CT, Murali A, Dong W, Srisathiyanarayanan D, Vaughan R, Ortiz-Alacantara J, Bhardwaj K, Li X, Li P & Kao CC (2009) Agonist and antagonist recognition by RIG-I, a cytoplasmic innate immunity receptor. J Biol Chem 284: 1155-65
  5. Chen C, Kao CC & Dragnea B (2008) Self-assembly of brome mosaic virus capsids: insights from shorter time-scale experiments. J Phys Chem A 112: 9405-12
  6. Ranjith-Kumar CT, Duffy KE, Jordan JL, Eaton-Bassiri A, Vaughan R, Hoose SA, Lamb RJ, Sarisky RT & Kao CC (2008) Single-stranded oligonucleotides can inhibit cytokine production induced by human toll-like receptor 3. Mol Cell Biol 28: 4507-19
  7. Chinnaswamy S, Yarbrough I, Palaninathan S, Kumar CT, Vijayaraghavan V, Demeler B, Lemon SM, Sacchettini JC & Kao CC (2008) A locking mechanism regulates RNA synthesis and host protein interaction by the hepatitis C virus polymerase. J Biol Chem 283: 20535-46
  8. Murali A, Li X, Ranjith-Kumar CT, Bhardwaj K, Holzenburg A, Li P & Kao CC (2008) Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response. J Biol Chem 283: 15825-33
  9. Aniagyei SE, Dufort C, Kao CC & Dragnea B (2008) Self-assembly approaches to nanomaterial encapsulation in viral protein cages. J Mater Chem 18: 3763-3774
  10. Bhardwaj K, Palaninathan S, Alcantara JM, Yi LL, Guarino L, Sacchettini JC & Kao CC (2008) Structural and functional analyses of the severe acute respiratory syndrome coronavirus endoribonuclease Nsp15. J Biol Chem 283: 3655-64
  11. Huang X, Bronstein LM, Retrum J, Dufort C, Tsvetkova I, Aniagyei S, Stein B, Stucky G, McKenna B, Remmes N, Baxter D, Kao CC & Dragnea B (2007) Self-assembled virus-like particles with magnetic cores. Nano Lett 7: 2407-16
  12. Ranjith-Kumar CT, Miller W, Sun J, Xiong J, Santos J, Yarbrough I, Lamb RJ, Mills J, Duffy KE, Hoose S, Cunningham M, Holzenburg A, Mbow ML, Sarisky RT & Kao CC (2007) Effects of single nucleotide polymorphisms on Toll-like receptor 3 activity and expression in cultured cells. J Biol Chem 282: 17696-705
  13. Gopinath K & Kao CC (2007) Replication-independent long-distance trafficking by viral RNAs in Nicotiana benthamiana. Plant Cell 19: 1179-91
  14. Sun J, DuFort C, Daniel MC, Murali A, Chen C, Gopinath K, Stein B, De M, Rotello VM, Holzenburg A, Kao CC & Dragnea B (2007) Core-controlled polymorphism in virus-like particles. Proc Natl Acad Sci U S A 104: 1354-9
  15. Ranjith-Kumar CT, Miller W, Xiong J, Russell WK, Lamb R, Santos J, Duffy KE, Cleveland L, Park M, Bhardwaj K, Wu Z, Russell DH, Sarisky RT, Mbow ML & Kao CC (2007) Biochemical and functional analyses of the human Toll-like receptor 3 ectodomain. J Biol Chem 282: 7668-78
  16. Yi G, Gopinath K & Kao CC (2007) Selective repression of translation by the brome mosaic virus 1a RNA replication protein. J Virol 81: 1601-9
  17. Dixit SK, Goicochea NL, Daniel MC, Murali A, Bronstein L, De M, Stein B, Rotello VM, Kao CC & Dragnea B (2006) Quantum dot encapsulation in viral capsids. Nano Lett 6: 1993-9
  18. Bhardwaj K, Sun J, Holzenburg A, Guarino LA & Kao CC (2006) RNA recognition and cleavage by the SARS coronavirus endoribonuclease. J Mol Biol 361: 243-56
  19. 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
  20. Chen C, Kwak ES, Stein B, Kao CC & Dragnea B (2005) Packaging of gold particles in viral capsids. J Nanosci Nanotechnol 5: 2029-33
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