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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
1P01AI098681-01A1
Application #
8551973
Study Section
Special Emphasis Panel (ZAI1-LR-M (M2))
Project Start
Project End
Budget Start
2013-07-02
Budget End
2014-06-30
Support Year
1
Fiscal Year
2013
Total Cost
$71,488
Indirect Cost
$20,004
Name
Harvard University
Department
Type
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Lee, Jennifer S; Raja, Priya; Pan, Dongli et al. (2018) CCCTC-Binding Factor Acts as a Heterochromatin Barrier on Herpes Simplex Viral Latent Chromatin and Contributes to Poised Latent Infection. MBio 9:
Cabrera, Jorge Ruben; Charron, Audra J; Leib, David A (2018) Neuronal subtype determines HSV-1 Latency-Associated-Transcript (LAT) promoter activity during latency. J Virol :
Jiang, Yike; Leib, David (2017) Preventing neonatal herpes infections through maternal immunization. Future Virol 12:709-711
Kurt-Jones, Evelyn A; Orzalli, Megan H; Knipe, David M (2017) Innate Immune Mechanisms and Herpes Simplex Virus Infection and Disease. Adv Anat Embryol Cell Biol 223:49-75
Lutz, Gabriel; Jurak, Igor; Kim, Eui Tae et al. (2017) Viral Ubiquitin Ligase Stimulates Selective Host MicroRNA Expression by Targeting ZEB Transcriptional Repressors. Viruses 9:
Enquist, Lynn W; Leib, David A (2017) Intrinsic and Innate Defenses of Neurons: Détente with the Herpesviruses. J Virol 91:
Katzenell, Sarah; Cabrera, Jorge R; North, Brian J et al. (2017) Isolation, Purification, and Culture of Primary Murine Sensory Neurons. Methods Mol Biol 1656:229-251
Jiang, Yike; Patel, Chaya D; Manivanh, Richard et al. (2017) Maternal Antiviral Immunoglobulin Accumulates in Neural Tissue of Neonates To Prevent HSV Neurological Disease. MBio 8:
Pan, Dongli; Pesola, Jean M; Li, Gang et al. (2017) Mutations Inactivating Herpes Simplex Virus 1 MicroRNA miR-H2 Do Not Detectably Increase ICP0 Gene Expression in Infected Cultured Cells or Mouse Trigeminal Ganglia. J Virol 91:
Manivanh, Richard; Mehrbach, Jesse; Knipe, David M et al. (2017) Role of Herpes Simplex Virus 1 ?34.5 in the Regulation of IRF3 Signaling. J Virol 91:

Showing the most recent 10 out of 26 publications