Current research activities

Latency of α-herpesviruses is the focus of research in my laboratory. My laboratory is utilizing Bovine Herpes Virus 1 (BHV-1) and to a lesser extent Herpes Simplex Virus 1 (HSV-1) to study these virus host interactions. BHV-1 is a significant viral pathogen of cattle that can induce respiratory disease, abortion, or occasionally encephalitis, and is a causative agent of "Shipping Fever" or Bovine Respiratory Complex. BHV-1 is also frequently found in buffalo, a growing food animal source in the US. As a consequence of the pathogenic potential of BHV-1, the cattle industry suffers more than $500,000,000/year in losses. HSV-1 is the leading cause of corneal blindness due to an infectious agent and the most significant infectious agent that causes encephalitis. Epidemiological studies have suggested that HSV-1 is a cofactor in Alzheimer’s disease.

α-herpesviruses initiate infection in mucosal epithelial surfaces located in the eyes, nose, mouth, upper respiratory tract, or genital tract. Extensive viral gene expression occurs, virus is shed, and clinical symptoms are apparent. Virus then enters the peripheral nervous system, where it establishes a latent infection in sensory neurons. Viral DNA can persist in a latent state for the lifetime of the infected host or can periodically reactivate. In contrast to the 70-80 viral genes expressed in epithelial cells, viral gene expression is very restricted in latently infected neurons. The latency related (LR) gene for BHV-1 or the latency-associated transcript (LAT) for HSV-1 is the only viral genes abundantly expressed in latently infected neurons. LAT and LR-RNA are transcribed from the opposite strand of an immediate early gene (ICP0) that activates productive gene expression. A latent infection can be operationally divided into 3 distinct stages: 1) establishment, 2) maintenance, and 3) reactivation form latency. Reactivation from latency can lead to recurrent disease and regardless of the clinical outcome results in virus transmission. Therefore, latency is crucial for pathogenesis and virus transmission.

Selected Recent Publications

1. Papugani, A., T. Coleman, C. Jones, and L. Zhang. 2008. The interaction between KSHV RTA and cellular RBP-Jk and their subsequent DNA binding are not sufficient for activation of RBP-Jk. Virus_ Research, 131: 1-7.

2. Peng, W., O. Vitvitskaia, D. Carpenter, S.L. Wechsler, and C. Jones. 2008. Identification of two small RNAs within the first 1.5-kb of the herpes simplex virus type 1 (HSV-1) encoded latency-associated transcript (LAT). J Neurovirology, 14:41-52.

3. Perez, S., F. Meyer, K. Saira, A. Doster, and C. Jones. 2008. Premature expression of the latency-related (LR) RNA correlates with higher levels of beta-interferon RNA expression in productively infected cells. J. Gen. Virology 89: 1338 - 1345.

4. Geiser, V., S. Rose, and C. Jones. 2008. Bovine herpesvirus type 1 induces cell death by a cell type dependent fashion. Microbial Pathogenesis 44:459-466.

5. Liu. Z.F., M.C.S. Brum, A. Doster, C. Jones, and S.I. Chowdhury. 2008. A Bovine Herpesvirus Type 1 (BHV-1) Mutant Virus Specifying a Carboxyl Terminal Truncation of Glycoprotein E (gE) is Defective in Anterograde Neuronal Transport in Rabbits and Calves. J. Virology, 82:7432-7442.

6. Shen, W. and C. Jones. 2008. Open reading frame 2 encoded by the latency related gene of bovine herpesvirus 1 has anti-apoptosis activity in transiently transfected neuroblastoma cells. J. Virology, 82:10940-10945.

7. Saira, K., S. Chowdhury, N. Gaudreault, L. da Silva, G. Henderson, A. Doster, & C. Jones. 2008. The zinc RING finger of the bovine herpesvirus 1 encoded bICP0 protein is crucial for viral replication and virulence. J. Virology, 82:12060-12068.

8. Jin, L., D. Carpenter, M. Moerdyk-Schauwecker, A.L. Vanarsdall, N. Osorio, C. Hsiang, C. Jones, and S.L. Wechsler. 2008. Cellular FLIP can substitute for the herpes simplex virus type 1 LAT gene to support a wild type virus reactivation phenotype in mice. J. Neurovirology, 14:389-400.

9. Carpenter, D., S. Singh, N. Osorio, C. H., X. Jiang, L. Jin, C. Jones, and S.L. Wechsler. Mutation of a putative ribozyme site in the herpes simplex virus type 1 gene that encodes LAT does not decrease the viral reactivation phenotype. 2008. J. Neurovirology, 14:558-562.

10. Jones, C. and S. Chowdhury. 2008. A review of the biology of bovine herpesvirus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex, and development of improved vaccines. Adv in Animal Health, 8:187-205.

11. Jones, C. and E.M. Scholar. 2008. Viral Induced Encephalitis, Neuroimmune Pharmacology, T. Iketsu, H.E. Gendelman edts, p327-341 Springer.

12. Brum. M.C.S., C. Coats, B.R. Sangena, A. Doster, C. Jones, and S.I. Chowdhury. 2009.
Bovine herpesvirus type 1 (BoHV-1) anterograde neuronal transport from trigeminal ganglia to nose and eye requires glycoprotein E. J. Neurovirology, 15:1-6.

13. Saira, K., Y. Zhou, and C. Jones. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) associates with interferon regulatory factor 7 (IRF7), and consequently inhibits beta interferon promoter activity. J. Virology. 83:3977-3981.

14. Meyer, F. and C. Jones. C/EBP-alpha cooperates with bTIF to activate the bovine herpesvirus 1 immediate early transcription unit 1 promoter. J. Neurovirology 15:123-130.

15. Ellis, J., S. Gow, N. Goji, C. Jones, A. Workman, G. Henderson, G. Alaniz, and T. Meinert. Efficacy of a combination viral vaccine in protecting cattle from experimental infection with bovine herpesviruses-1 isolated from recent “vaccine breaks”. IN PRESS, J. of American Veterinary Medical Association.

16. Workman, A., S. Perez, A. Doster, and C. Jones. 2009. Dexamethasone treatment of calves latently infected with bovine herpesvirus 1 (BHV-1) leads to activation of the bICP0 early promoter, in part by the cellular transcription factor C/EBP-alpha. J. Virology, IN PRESS.

17. Jaber, T., G. Henderson, S. Li, G.-C. Perng, D. Carpenter, S. Wechsler, and C. Jones. Identification of a novel herpes simplex virus type 1 (HSV-1) transcript and protein (AL3) expressed during latency. J. Gen. Virology, IN PRESS.

18. Shen, S., M. Sa e Silva, T. Jaber, O. Vitvitskaia, S. Li, G. Henderson, and C. Jones. Two small RNAs encoded within the first 1.5 kb of the herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) can inhibit productive infection, and cooperate to inhibit apoptosis. J. Virology, IN PRESS.

Education

Bethany College, Lindsborg, KS
BA, Biology, Chemistry
1978

University of Kansas,
Lawrence, KS
PhD, Microbiology
1985

Linus Pauling Res. Inst.
Postdoc Fellow
1985-87

Professional Positions:

1996-
Professor: Dept of Veterinary & Biomedical Sciences
University of Nebraska-Lincoln, Lincoln, NE

1989-96
Associate Professor: Dept of Veterinary and Biomedical Sciences
University of Nebraska-Lincoln, Lincoln, NE

1987-89
Assistant Professor: Dept. of Microbiology
University of Mississippi Medical Center

1984-87
Post Doctoral Fellow: Laboratory of Viral Carcinogenesis
Linus Pauling Inst. of Science

Honors and Awards:

Panel Manager for USDA Virology Study Section, 1996 and 2001.

Panel Member for USDA Virology Study Section, 1993 and 1998.

Symposium Lecture on BHV-1 latency; International Herpesvirus Workshop (1996)
State of the Art Lecture on alpha-herpesvirus latency; ASV (1997)

ASV symposium lecture: Analysis of alpha-herpesvirus latency (2001).

European Society of Vet. Virology Symposium lecture: Analysis of BHV-1 latency and pathogenesis (2001).

European Society of Virology Symposium Lecture: Analysis of BHV-1 genes that are expressed in sensory neurons of latently infected cattle (2005).