Clinton Jones, Ph.D.

Charles Bessey Professor University of Nebraska-Lincoln Dept. of Vet and Biomedical Sciences 103 VBS Lincoln, NE 68583-0905 Phone - 402.472.1890 Fax - 402.472.9690 cjones@unlnotes.unl.edu

STATEMENT OF 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 PUBLICATIONS IN REFEREED JOURNALS (2003-present):

1. Jones, C. Analysis of HSV-1 and BHV-1 1 latency. 2003. Clinical Microbiology Reviews. 16:79-95

2. Lovato, L., M. Inman, G. Henderson, A. Doster., and C. Jones, C. 2003. Infection of cattle with a bovine herpesvirus 1 (BHV-1) strain that contains a mutation in the latency related gene leads to increased apoptosis in trigeminal ganglia during the transition from acute infection to latency. J of Virology, 77:4848-4857.

3. Geiser, V. and C. Jones. 2003. Stimulation of bovine herpesvirus 1 productive infection by the adenovirus E1A gene and the cellular transcription factor E2F4. J. of General Virology, 84:929-938.
4. Jin, L., W. Peng, G-C Perng, A.B. Nesburn, C. Jones, and S.L. Wechsler. 2003. Identification of herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) sequences that both inhibit apoptosis and enhance the spontaneous reactivation phenotype. J of Virology, 77:6556-6561.

5. Mott, K., N. Osorio, L. Jin, D. Brick, J. Naito, J. Cooper, G. Henderson, M. Inman, C. Jones, S. L. Wechsler, and G.-C. Perng. 2003. The BHV-1 LR gene’s ability to restore the high reactivation phenotype to an HSV-1 LAT null mutant appears to be due to its anti-apoptosis function. Journal of General Virology, 84:2975-2985.

6. Peng, W. G. Henderson, G.-C Perng, A.B. Nesburn, S.L. Wechsler, and C. Jones. 2003. The gene that encodes the herpes simplex virus type 1 (HSV-1) latency associated transcript (LAT) influences the accumulation of the transcripts (Bcl-xL and Bcl-xS), that encode apoptotic regulatory proteins. Journal of Virology, 77:10714-10718.

7. Devireddy, L., Y. Zhang, and C. Jones. 2003. Cloning and initial characterization of an alternatively spliced transcript encoded by the bovine herpes virus 1 latency related (LR) gene. Journal of Neurovirology, 9: 612-622.

8. Henderson, G., G.-C. Perng, A. B. Nesburn, S. L. Wechsler, and C. Jones. 2004. The latency related (LR) gene encoded by bovine herpesvirus 1 (BHV-1) can suppress caspase 3 and caspase 9 cleavage during productive infection. J. of Neurovirology. 10:64-70.

9. Jiang, Y., M. Inman, Y. Zhang, N. A. Posadas , and C. Jones. 2004. A mutation in the latency related gene of bovine herpesvirus 1 (BHV-1) inhibits expression of proteins encoded by ORF2 and Reading Frame C during productive infection. J. of Virology 78:3184-3189.

10. Inman, M., J. Zhou, H. Webb, and C. Jones. 2004. Identification of a novel transcript containing a small open reading frame that is expressed during latency, and is antisense to the latency related gene of bovine herpes virus 1 (BHV-1). J. of Virology 78:5438-5447.

11. L Jin, GC Perng, DJ Brick, J Naito, AB Nesburn, C Jones, and SL Wechsler. 2004. Methods for detecting the HSV-1 LAT anti-apoptosis activity in Infected Tissue Culture cells. Journal of Virological Methods 118:9-13.

12. Henderson, G., Y. Zhang, M. Inman, D. Jones and C. Jones. 2004. Infected cell protein 0 encoded by bovine herpesvirus 1 can activate caspase 3 when overexpressed in transfected cells. J Gen Virol ; 85: 3511-3516

13. Peng, W., L. Jin, G. Henderson, G.C. Perng, D.J. Brick, A.B. Nesburn, S.J. Wechsler, and C. Jones. 2004. Mapping herpes simplex virus type 1 (HSV-1) LAT sequences that protect from apoptosis mediated by a plasmid expressing caspase-8. Journal of Neurovirology, 10:260-265.

14. Perez, S., M. Inman, A. Doster, and C. Jones. 2005. The latency related gene encoded by bovine herpesvirus 1 (BHV-1) promotes virus growth and reactivation from latency in tonsils of infected calves. J. of Clinical Microbiology. 43: 393-401.

15. Barsam, C.A, DJ. Brick, C Jones, SL Wechsler, G-C Perng. 2005. A viral model for corneal scarring and neovascularization following ocular infection of rabbit with a herpes simplex virus type 1 (HSV-1) mutant. Cornea, IN PRESS.

16. Zhang, Y. and C. Jones. Identification of functional domains within the bICP0 protein encoded by BHV-1. J. of General Virology, IN PRESS.

17. Peng, W., G. Henderson, M. Inman, L. BenMohamed, G.-C. Perng, S. L. Wechsler, and Clinton Jones. 2005. The locus encompassing the latency-associated transcript (LAT) of herpes simplex virus type 1 interferes with and delays interferon expression in productively infected neuroblastoma cells and trigeminal ganglia of acutely infected mice. J. of Virology, IN PRESS.