During the initial 0-24 hours of viral infection, many viruses cause down-regulation of gap junctional communication among infected cells. Research covered in this proposal is aimed at developing the technique of monitoring and exploring the mechanism of this gap junctional down-regulation using electrophysiological and biochemical methods. Specifically, we hope to utilize these techniques to study the early events of viral infection, and to determine how they cause down-regulation of gap junctional intercellular communication. A major advantage of electrophysiological monitoring is that it allows following and quantifying in vitro in living cells at the early stages of viral infection, before cytopathic effects become visible. In almost all viral infections, attachment of the infecting virus to the susceptible cell must occur via complementary molecules on the virus and the cell. While the immediate surface interactions between virus and receptors have been studied, it has been difficult to ascertain if any other aspects of host cell physiology are concurrently affected. Entry of the virus into the cellular interior follows attachment. As with attachment, this second step (penetration) is also largely ignored with respect to changes in the physiology of the host cell. Once penetration ends, uncoating unravels the viral genome and a very orderly expression of genes ensues. For HSV there are three waves of gene expression. The early gene products are believed to control the entire process of viral replication, and they also affect the cellular machinery. We plan to take advantage of the easily quantifiable changes in electrical coupling to study such early events of viral infection as attachment, entry and early activation of viral genome. Furthermore, we will take advantage of these techniques to investigate specifically how the virus effects gap junctions, and how important to infectivity is closure of these channels of intercellular communication.
| Miezeiewski, Blair; McShane-Kay, Kerry; Woodruff, Richard I et al. (2012) Role of adherens junction proteins in differential herpes simplex virus type 2 infectivity in communication-competent and -deficient cell lines. Intervirology 55:465-74 |
| Knabb, Maureen T; Danielsen, Casey A; McShane-Kay, Kerry et al. (2007) Herpes simplex virus-type 2 infectivity and agents that block gap junctional intercellular communication. Virus Res 124:212-9 |
