Dr. David Brian

Major Research Interests

We are interested in defining the molecular events that occur during coronavirus RNA genome replication and during the replication of subgenomic RNA replicons.  By defining cis- and trans-acting factors involved in the regulation of RNA replication and gene expression, we hope to understand the molecular basis for the switch from acute lytic to persistent nonlytic infection that seems to accompany development of coronavirus-induced chronic disease in animals and humans. This information will be used to try to design therapeutic molecules that block virus replication altogether. We are also trying to develop the subgenomic replicon as a novel vector for the expression of foreign genes in animal and human cells.

Selected Publications

Sethna, Phiroze B., Shan-Ling Hung, and David A. Brian.  1989.  Coronavirus subgenomic minus-strand RNA and the potential for mRNA replicons.  Proc. Natl. Acad. Sci., U.S.A.  86:5626-5630.

Hofmann, Martin A., Phiroze B. Sethna, and David A. Brian.  1990.  Bovine coronavirus mRNA replication continues throughout persistent infection in cell culture.  J. Virology  64:4108-4114.

Sethna, Phiroze B., Martin A. Hofmann, and David A. Brian.  1991.  Minus-strand copies of replicating coronavirus mRNAs contain antileaders.  J. Virol.  65:320-325. 

Hofmann, Martin A., and David A. Brian.  1991.  The 5-prime end of coronavirus minus-stand RNAs contain a short poly(U) tract.  J. Virol.  65:6331-6333.

Tung, Frank Y. T., Sushma Abraham, Manjiri Sethna, Shan-Ling Hung, Phiroze B. Sethna, Brenda G. Hogue, and David A. Brian.  1992.  The 9.1 kilodalton hydrophobic protein encoded at the 3' end of the porcine transmissible gastroenteritis coronavirus genome is membrane associated.  Virology  186:676-683.

Senanayake, Savithra D., Martin A. Hofmann, Joanne L. Maki, and David A. Brian.  1992.  The nucleocapsid protein gene of the bovine coronavirus is bicistronic.  J. Virol. 66:5277-5283.

Hofmann, Martin A., Ruey-Yi Chang, Seulah Ku, and David A. Brian.  1993.  Leader-mRNA junction sequences are unique for each subgenomic mRNA species in the bovine coronavirus and remain so throughout persistent infection.  Virology, 196:163-171.

Hofmann, Martin A., Savithra D. Senanayake, and David A. Brian.  1993.  A translation-attenuating intraleader open reading frame is selected on coronavirus mRNAs during persistent infection.  Proc. Natl. Acad. Sci. USA, 90:11733-11737.

Brian, David A., Ruey-Yi Chang, Phiroze B. Sethna, and Martin A. Hofmann.  1994.  Role of subgenomic minus-strand RNA in coronavirus replication.  In:  M. A. Brinton, C. H. Calisher, and R. Rueckert (eds.).  Positive-Strand RNA Viruses.  Arch. Virol., Supplementum 9:173-180.

Chang, Ruey-Yi, Martin A. Hofmann, Phiroze B. Sethna, and David A. Brian.  1994.  A cis-acting function for the coronavirus leader in defective-interfering RNA replication.  J. Virol.  68:8223-8231.

Chang, Ruey-Yi, and David A. Brian.  1996.  Cis-requirement for N-specific protein sequence in bovine coronavirus defective interfering RNA replication.  J. Virol. 70:2201-2207.

Chang, Ruey-Yi, Rajesh Krishnan, and David A. Brian.  1996.  The UCUAAAC promoter motif is not required for high frequency leader recombination in bovine coronavirus defective interfering RNA.  J. Virol.  70:2720-2729.

Krishnan, Rajesh, Ruey-Yi Chang, and David A. Brian.  1996.  Tandem placement of a coronavirus promoter results in enhanced mRNA synthesis from the downstream-most initiation site.  Virology. 218:400-405.

Senanayake, Savithra D., and David A. Brian.  1997.  Bovine coronavirus I protein synthesis follows ribosomal scanning on the bicistronic N mRNA.  Virus Research 48:101-105.

Sethna, Phiroze B., and David A. Brian.  1997.  Coronavirus subgenomic and genomic minus-strand RNAs copartition in membrane-protected replication complexes.  J. Virol. 71:7744-7749.

Brian, David A., and Willy Spaan.  1997.  Recombination and coronavirus defective interfering RNAs. Seminars in Virology 8:101-111.

O’ Connor, Jennifer B., and David A. Brian. 1999. The major product of procine transmissible gastroenteritis coronavirus gene 3b is an integral membrane glycoprotein of 31 kDa. Virology 256:152-161.

Senanayake, Savithra D., and David A. Brian. 1999. Translation from the 5’ UTR of mRNA 1 is repressed, but that from the 5’ UTR of mRNA 7 is stimulated in coronavirus infected cells.  J.Virol. 73:8003-8009.

Williams, Gwyn D., Ruey-Yi Chang, and David A. Brian. 1999.  A phylogenetically conserved hairpin-type 3’ UTR pseudoknot functions in coronavirus RNA replication. J. Virol. 73:8349-8355.

O’ Connor, Jennifer B., and David A. Brian. 2000. Downstream ribosomal entry for translation of coronavirus TGEV gene 3b. Virology 269:172-182.

Brian, David A. 2001. Nidovirus genome replication and subgenomic mRNA synthesis: Pathways followed and cis-acting sequences required: a review.  Adv. Exp. Biol. Med. 494:415-428.

Ozdarendeli, Aykut., Seulah Ku, Sylvie Rochat, Gwyn D. Williams, Savithra D. Senanayake, and David A. Brian. 2001. Downstream sequences influence the choice between a naturally occurring noncanonical and closely positioned upstream heptameric fusion motif during bovine coronavirus subgenomic mRNA synthesis.  J. Virol. 75:7362-7374.

Raman, Sharmila, Peter Bouma, Gwyn D. Williams, and David A. Brian. 2003. Stem-loop III in the 5’ UTR is a cis-acting element in bovine coronavirus DI RNA replication.  J. Virol. 77:6720-6730.

Wu, Hung-Yi, James S. Guy, Dongwon Yoo, Reinhard Vlasak, Ena Urbach, and David A. Brian. 2003. Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavirus molecules.  Virology 315:174-183 .

Dr. David Brian

Professor
D.V.M., 1969, Michigan State University;
Ph.D., 1974, Michigan State University

M409 Walters Life Sciences Knoxville, Tennessee
37996-0845

Phone: 865-974-4030
Fax: 865-974-4007
Email: dbrian@utk.edu