Clinton Jones, Ph.D.
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 Recent Publications: 1. Peng, W., O. Vitvitskaia, D. Carpenter, S.L. Wechsler, and C. Jones. 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, In Press, 2007. 2. Carpenter, D., C. Hsiang, L. Jin, N. Osorio, L. BenMohamed, C. Jones, and S.L. Wechsler. Stable cell lines expressing high levels of the herpes simplex virus type 1 LAT are refractory to caspase 3 activation and DNA laddering following cold shock induced apoptosis. Virology, In Press, 2007. 3. Xu, D., J. Zhang, T. Coleman, A. Fagot, C. Kotalik, L. Zhao, C. Jones, and L. Zhang. A regulatory loop between Kaposi’s sarcoma-associated herpesvirus replication and transcription activator (RTA) and Epstein-Barr virus latent membrane protein 1 (LMP-1). J Virology 81:6068-6078, 2007. 4. Jin, L., G.-C. Perng, D. Carpenter, K. R. Mott, N. Osorio, J. Naito, D.J. Brick, C. Jones, and S.L. Wechsler . Reactivation Phenotype in Rabbits of a Herpes Simplex Virus Type 1 (HSV-1) Mutant Containing an Unrelated Anti-Apoptosis Gene in Place of LAT. J Neurovirol 13: 78-84, 2007. 5. Perez, S., F. Meyer, G. Henderson, Y. Jiang, S. Sherman, A. Doster, M. Inman, and C. Jones. A protein encoded by the bovine herpesvirus 1 ORF E gene induces neurite-like morphological changes in mouse neuroblastoma cells and is expressed in trigeminal ganglionic neurons. J Neurovirol, 13:139–149, 2007. 6. Saira, K. and C. Jones. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 (IRF3), and consequently inhibits beta interferon promoter activity. J Virology 81:3077-3086, 2007. 7. Horiba, M., L.B. Martinez, J.L. Buescher, S. Sato, J. Limoges, J. Jiang, C. Jones, and T. Ikezu. OTK18, a zinc finger protein, regulates HIV LTR through two distinct regulatory regions. J Gen Virol, 88:236-241, 2007. 8. Meyer, F., S. Perez, V. Geiser, M. Sintek, M. Inman, & C. Jones. A protein encoded by the bovine herpes virus 1 (BHV-1) latency related gene interacts with specific cellular regulatory proteins, including the CCAAT enhancer binding protein alpha (C/EBP-a). J Virol 81:59-67, 2007. 9. Jones, C., V. Geiser, G. Henderson, Y. Jiang, F. Meyer, S. Perez, Y. Zhang. Functional analysis of bovine herpesvirus 1 (BHV-1) genes expressed during latency. Vet Micro 113:199-210, 2006. 10. Perez, S. L. Lovato, J. Zhou, A. Doster & C. Jones. Comparison of inflammatory infiltrates in trigeminal ganglia of cattle infected with wild type BHV-1 versus a virus strain containing a mutation in the LR (latency-related) gene. J Neurovirol, 12:392-397, 2006. 11. Morishige, N., J.V. Jester, J. Naito, N. Osorio, A. Wahlert, C. Jones, R.D. Everett, S.L. Wechsler, and G. C. Perng. HSV-1 ICP0 localizes in the stromal layer of infected rabbit corneas and predominantly resides in the cytoplasm and/or perinuclear region of rabbit keratocytes. J Gen Virol 87:2817-2825, 2006. 12. Zhang, Y., Y. Jiang, J. Zhou, V. Geiser, & C. Jones. The bovine herpes virus 1 (BHV-1) immediate early protein (bICP0) interacts with the histone acetyltransferase p300, and these interactions correlate with stimulation of gC promoter activity. J Gen Virol 87: 1843-1851, 2006.
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