Professor
Vet & Biomedical Sciences 234 MOLR, UNL, 68583-0900
402 472 1890
cjones2@unl.edu Download vCard | Introduction: | I have been a faculty member since 1987, and have been funded by federal granting agencies (USDA and/or NIH) for every year except the first. The research of my laboratory has been primarily focused on viral pathogenesis. To date, the research from my laboratory has resulted in 126 papers that are published or are in press. Most of these articles have been published in virology journals (J. of Virology, J. of General Virology, J. of Neurovirology, or Virology for example). We have also published numerous papers in journals that are not focused on virology (Science, PNAS, Nucleic Acids Research, Cancer Research, and J. Biol. Chem for example). Our research has been recognized at national and international levels. For example, I have been invited to present symposium talks at the American Society of Virology meeting twice, International Herpesvirus Workshop on several occasions, European Society of Veterinary Virology twice, Cold Spring Harbor Symposium on Viral Pathogenesis, American College for Veterinary Pathologists, and International Society of Neurovirology. My research program has been very interactive. I have collaborated with several herpes virologists (Steve Wechsler at UC-Irvine, Oscar Perng at Emory, Sri Srikumaran, at Washington State, Luwen Zhang at UNL, and Shafiq Chowdhury at LSU). I have also collaborated with Fernando Ororio at UNL, a plant scientist (Marty Dickman who is at Texas A&M), several cancer biologists (Marvin Cuchens who is now retired, Abdur Razzaque who is at the FDA, and Joe DiPaolo who was at NCI), and a veterinary diagnostic pathologist (Alan Doster who is at UNL).
| Expertise: | 1. Virus host interactions in cultured cells and animal models.
2. Latent and persistent virus infections.
3. Innate immune responses to virus infection.
4. Analysis of how viral genes regulate cellular apoptosis pathways.
5. Regulation of viral gene expression.
6. Vaccine development.
| Teaching: | 1. Introduction to Molecular Virology and Viral Pathogenesis (852): This course has been taught in the fall of even numbered years and is intended to introduce graduate students to the basic virus groups. Included in the discussion of the respective virus groups are replication strategies, regulation of viral gene expression, and mechanisms of pathogenesis. The course also discusses basic concepts of viral genetics, methodology used to study viruses, and virus-host interactions. This course is a lecture course. I have team taught this course since 1990 and have given 60% of the lectures.
2. Medical Molecular Virology (950): This course has been taught in the fall of odd numbered years. It is an in depth study of selected topics that pertain to current research in virology. The format of the course relies heavily on students presenting research papers and discussing these papers. Formal lectures are given by the instructor to introduce each topic. I have team taught this course since 1991 and I teach 50% of the classes.
3. Signal Transduction (964): This course is an in depth survey of signal transduction that focuses primarily on mammalian systems. The format of the course is that topics are introduced by a lecture from the instructor. Current papers are then assigned, and discussed by the class. I have been teaching this course since 1994.
| Research: | Latency of alpha-herpesvirinae subfamily members, bovine herpes virus 1 (BHV-1 and herpes simplex virus type 1 (HSV-1), is a major focus of my research program. We have focused on identifying and characterizing viral gene products that are expressed in latently infected sensory neurons. It is now clear that the latency related (LR) gene of BHV-1 and HSV-1 LAT (latency associated transcript) encode anti-apoptosis functions, which promote survival of infected neurons. A protein encoded by the LR gene also interacts with at least three cellular transcription factors, Notch1, Notch3, and c/EBP-alpha. We believe these interactions promote the establishment and maintenance of latency by extinguishing viral gene expression. LAT and the LR gene also encode several non-coding small RNAs that interfere with expression of specific viral genes, ICP0 and ICP4 for example. The ability of LAT and the LR gene to promote survival of infected neurons and interfere with productive infection is crucial for maintaining a life-long latent infection in the natural host.
The second focus of my lab is to understand the function of the BHV-1 infected cell protein 0 (bICP0). The bICP0 protein activates expression of all viral genes, is constitutively expressed during productive infection, inhibits interferon dependent transcription, and consequently stimulates productive infection. Site specific mutagenesis and transposon insertion mutagenesis have revealed four separate domains in bICP0 that activate transcription: 1) the zinc RING finger located between amino acids 13-51, 2) a large domain spanning amino acids 78-265, 3) sequences at or near amino acid 457, and 4) a nuclear localization signal at the C-terminus. In addition to activating viral gene expression, bICP0 interacts with chromatin remodeling enzymes (histone deacetylase 1 and p300, a histone acetyltransferase), and inhibits interferon (IFN) dependent transcription. A bacterial artificial chromosome containing the BHV-1 genome has been used to develop bICP0 zinc RING finger mutants. As expected, these bICP0 mutants do not grow efficiently in cultured cells. Our long-term goals are to delineate the mechanism by which bICP0 stimulates viral gene expression, productive infection, and reactivation from latency. Constructing a bICP0 mutant that allows efficient growth in cultured cells, but is not as pathogenic has potential to serve as an improved modified live vaccine.
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