Faculty & Staff
Arthur R. Frampton, Jr., Associate Professor
Ph.D., Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, 2002
B.S., Cell Biology, University of Tennessee, Knoxville, TN, 1994
Dobo Hall 110 | (910) 962-2643 | 601 South College Road, Wilmington, NC 28403-5915
Equine herpesvirus 1 (EHV-1) is a ubiquitous pathogen of horses. Most horses are exposed to the virus within 6-12 months after birth and are frequently re-infected throughout their lifetime. The virus is readily spread from horse to horse via nasal secretions and contact with infected surroundings. EHV-1 initiates infection within the upper respiratory tract and subsequently is transmitted throughout the body by infected T cells, monocytes, and macrophages. Clinical signs that appear early after infection include fever, inappattence, malaise, coughing, and mucopurulent discharge. As the infection progresses, horses may exhibit signs of serious neurological illness including ataxia, disorientation, and partial to full paralysis. In addition to the serious neurological sequelae, EHV-1 is also a serious threat to pregnant mares. As EHV-1 spreads from the respiratory tract to other parts of the body, the sensitive endometrium of pregnant mares can become infected. Infection of endothelial cells at this sensitive tissue site can lead to thrombosis and vasculitis, which deprives the fetus of oxygen. Significant infection and subsequent damage in the endometrium results in the expulsion of a stillborn fetus. Due to the lack of success of various EHV-1 vaccination programs over the years, we strongly propose that the best way to combat EHV-1 transmission and pathogenesis in the horse population is to interrupt the virus life-cycle before the virus has the opportunity to cause serious damage to the equine. The successful intervention and prevention of EHV-1 induced sequelae requires the following. First, appropriate surveillance measures must be in place to detect an outbreak of EHV-1 on a particular farm or within a stable of horses. These measures include the frequent monitoring of horses for any signs of respiratory distress that may be indicative of an EHV-1 infection. Once an infection is suspected, quick screening assays should be employed to confirm that EHV-1 is the responsible pathogen. Once EHV-1 is confirmed, the next step would be to administer drugs or small molecule inhibitors that would effectively interfere with or stop EHV-1 from progressing.
Current research in my lab focuses on elucidating the signaling pathways and cell factors that are critical for a productive EHV-1 infection to occur. We previously identified a cellular kinase, ROCK1, which is essential for EHV-1 infection. Research in this area will be extended to examine how ROCK1 is activated by EHV-1, what specific cellular events are reliant upon this activation, and how these cellular events contribute to a productive infection. In addition, further studies will aim to identify additional cellular factors that are required for EHV-1 infection.
Another avenue of research in my laboratory is the identification of an EHV-1 entry receptor or receptors. In order to identify an EHV-1 entry receptor, I will employ an equine cDNA library that is inserted into a retrovirus vector. Pools of this library will be used to infect EHV-1-resistant cells. These cells will then be infected with an EHV-1 virus that expresses GFP. Pools of the library that give positives will be further subdivided until infection with single cDNA pools enable entry of EHV-1. At this stage the cDNA will be amplified using primers that flank the cDNA insert. The PCR products will then be cloned into a plasmid and sequenced. Once potential entry receptors are identified, further assays, such as antibody, soluble receptor, and siRNA inhibition of EHV-1 infection, will be used to verify that the identified protein is an EHV-1 receptor.
Membership in Professional Societies:
American Society for Virology
American Society of Gene Therapy
Arthur R. Frampton Jr., P.M. Smith, Y. Zhang, T. Matsumura, N. Osterrieder, and D.J. O’Callaghan. Contribution of Gene Products Encoded Within the Unique Short Segment of Equine Herpesvirus 1 to Virulence in a Murine Model. (2002) Virus Research 90: 287-301.
Yunfei Zhang, P.M. Smith, A.R. Frampton Jr., N. Osterrieder, S.R. Jennings, and D.J. O’Callaghan. Determination of Cytokine Profiles and Long Term Virus-Specific Antibodies Following Immunization of CBA Mice with Equine Herpesvirus 1 and Viral Glycoprotein D. (2003) Viral Immunology 16: 307-320.
Arthur R. Frampton Jr., P.M. Smith, Y. Zhang, W.D. Grafton, T. Matsumura, N. Osterrieder, and D.J. O’Callaghan. Meningoencephalitis in Mice Infected with an Equine Herpesvirus 1 Strain KyA Recombinant Expressing Glycoprotein I and Glycoprotein E. (2004) Virus Genes 29: 9-17.
Arthur R. Frampton Jr., W.F. Goins, J.B. Cohen, J. von Einem, N. Osterrieder, D.J. O’Callaghan, and J.C. Glorioso. Equine Herpesvirus 1 (EHV-1) Utilizes a Novel Herpesvirus Entry Receptor. (2005) Journal of Virology 79:3169-3173.
Arthur R. Frampton Jr., W.F. Goins, K. Nakano, E.A. Burton, and J.C. Glorioso. (Review) HSV Trafficking and Development of Gene Therapy Vectors with Applications in the Nervous System. (2005) Gene Therapy 12:891-901.
Marianna Tsvitov, A.R. Frampton Jr., W.A. Shah, Z. Kapacee, A. Ozuer, S.K. Wendell, W.F. Goins, J.B. Cohen, and J.C. Glorioso. Soluble Gycoprotein D (gD) Mediates Entry of gD-Deficient HSV-1 Particles. (2007) Virology 360:477-491.
Arthur R. Frampton Jr., D.B. Stolz, H. Uchida, W.F. Goins, J.B. Cohen, and J.C. Glorioso. Equine Herpesvirus 1 Enters Cells by Two Different Pathways and Infection Requires the Activation of the Cellular Kinase ROCK1. (2007) Journal of Virology 81:10879-10889.
Darren Wolfe, W.F. Goins, A.R. Frampton Jr., M. Mata, D.J. Fink, and J.C. Glorioso. (Book Chapter) Therapeutic Gene Transfer with Replication Defective Herpes Simplex Viral Vectors. (2008) In: Gene Therapy:Therapeutic Mechanisms and Strategies
Arthur R. Frampton Jr., H. Uchida, J. von Einem, W. F. Goins, P. Grandi, J. B. Cohen, N. Osterrieder, J. C. Glorioso. Equine Herpesvirus Type 1 (EHV-1) Induces the Stabilization of Microtubules and Microtubular Transport and Nuclear Accumulation of Nucleocapsids is Dependent on Dynein and ROCK1 Activation. (2008) In preparation.
Hiroaki Uchida, W. A. Shah, A. Ozuer, A.R. Frampton Jr., W.F. Goins, P. Grandi, S.C. Watkins, J.B. Cohen, and J.C. Glorioso. Establishment and Characterization of HVEM-Selective HSV-1 Mutants. (2008) In preparation.