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David J. Barton, Ph.D.

Professor of Immunology & Microbiology

12800 E. 19th Ave., RC-1 N 9116
Mail Stop 8333, Aurora, CO 80045

Phone: (303) 724-4215

David J. Barton, Ph.D., earned his doctoral degree from the University of Toledo (formerly the Medical College of Ohio) in 1989. He completed 7 years of postdoctoral research training at the University of Florida in Gainesville, Florida.

Dr. Barton joined the faculty of the University of Colorado School of Medicine Department of Microbiology in 1997.

My primary interests concern the molecular mechanisms of picornavirus replication and the evasion of interferon by hepatitis C virus.

Positive-strand RNA viruses like picornaviruses and hepatitis C virus are interesting because they replicate exclusively via RNA intermediates. Considering the "RNA World" view of the evolution of life, RNA viruses represent modern day organisms with evolutionarily ancient replication strategies. Positive-strand viral RNA serves two important functions within the cytoplasm of infected host cells:
(1) as mRNA for the expression of the viral proteins and,
(2) as the template for negative-strand RNA synthesis.
Viral RNA cannot simultaneously serve as a mRNA and as a template for negative-strand RNA synthesis due to the 5' to 3' movement of translating ribosomes on the viral mRNA and the 3' to 5' movement of replicase during negative-strand RNA synthesis. Communication between 5' and 3' terminal RNPs of viral RNA provides mechanisms to avoid ribosome-replicase collisions.

Poliovirus RNA, as mRNA, first becomes part of a messenger ribonucleoprotein (mRNP) complex with communication between the 5'- and 3'-termini mediated by the cellular translation machinery (eIF4G, poly (A) binding protein, poly (C) binding protein, etc.). Following viral protein synthesis, the viral mRNP complex must transform into a preinitiation RNA replication complex to allow for viral RNA replication. Poliovirus 2CATPase appears to mediate interactions between seemingly distal RNP complexes in poliovirus RNA to accomplish viral RNA replication. Our recently published model of poliovirus RNA replication (J. Virol. 2003), emphasizing communication between distally located RNP structures, is broadly applicable to all positive-strand RNA animal viruses.

In another series of experiments we discovered that hepatitis C virus RNA is detected and destroyed by an interferon-regulated antiviral pathway present in the cytoplasm of cells; the 2'-5' oligoadenylate synthetase/ribonuclease L pathway. Ribonuclease L cleaves viral RNA at single-stranded UA and UU dinucleotides. Relatively interferon-resistant genotype 1 hepatitis C viruses have fewer ribonuclease L cleavage sites than more interferon-sensitive genotype 2 and 3 viruses. These discoveries help to explain the clinical outcomes of interferon therapy in hepatitis C virus-infected patients where patients infected with genotype 1 viruses are cured less frequently by interferon therapy than patients infected with genotype 2 or 3 viruses.

Dr. Barton's Current NIH Research Grants

Dr. Barton has received many awards and honors throughout his career, including being an American Cancer Society Research Scholar from 2006-2008. He received two Excellence in Teaching Awards from the School of Medicine in 2000-2001 and 2003-2004.  Dr. Barton has served on the Editorial Board of the Journal of Virology and provided journal reviews for numerous scientific publications.  He has served as a grant reviewer for NIH, ACS, and other funding organizations.