The long term objectives of this Program Project are to elucidate host and viral mechanisms that tilt the interaction of herpes simplex virus (HSV) and neurons either towards lytic infection or towards latency. HSV latency is the most fascinating biological property ofthe virus and its most important clinical feature, and understanding HSV latency may lead to new therapies or even a cure for this widespread pathogen. All three projects use mice to study latency. The mouse core provides animals to the investigators in these projects. Additionally, it ensures uniform practices in the inoculation, treatment, and handling of mice and mouse tissues for Projects 1, 2, and 3, so that results from one project can be directly compared to those from the other projects. Standard protocols have been created that include a single wild type strain of virus from which mutants are derived, and a common mouse strain for studies that do not require inbred strains. Specific methods for minimizing pain and discomfort, including anesthesia and euthanasia also ensure uniformity. The core thus provides a high-quality cost-effective means of testing HSV-1 wild type and mutant viruses in vivo for the parameters of latency and reactivation and of providing trigeminal ganglia tissue for analyses and for cultured neurons for in vitro latency studies. By having centralized oversight, the Program may avoid duplication of experiments and unnecessary use of animals.
By providing a means of testing in vivo for parameters of latency and reactivation and of providing trigeminal ganglia tissue for cultured neurons for in vitro latency studies, the mouse core facilitates research to understand herpes simplex virus (HSV) latency. Understanding HSV latency might lead to new treatments or even cures for HSV infections, which are widespread and, in some cases, life-threatening.
|Jurak, Igor; Hackenberg, Michael; Kim, Ju Youn et al. (2014) Expression of herpes simplex virus 1 microRNAs in cell culture models of quiescent and latent infection. J Virol 88:2337-9|
|Pan, Dongli; Flores, Omar; Umbach, Jennifer L et al. (2014) A neuron-specific host microRNA targets herpes simplex virus-1 ICP0 expression and promotes latency. Cell Host Microbe 15:446-56|
|Rosato, Pamela C; Leib, David A (2014) Intrinsic innate immunity fails to control herpes simplex virus and vesicular stomatitis virus replication in sensory neurons and fibroblasts. J Virol 88:9991-10001|