Once an individual is infected with herpes simplex virus (HSV), the virus establishes a latent infection in sensory neurons. Periodically, various stimuli may induce lytic reactivation resulting in mild recurrent lesions to more severe disease. The factors which determine the establishment of latency and reactivation are poorly understood. However, the regulation of this latency-reactivation cycle is dependent upon the components which regulate the expression of the IE genes. The critical component of this regulatory process is HCF-1. Analyses of this protein in a mouse model have shown that the protein is specifically sequestered in the cytoplasm of sensory neurons and rapidly transported to the nucleus in response to reativation stimuli. Studies have determined that the nuclear transport of HCF-1 in latently infected neurons correlates with viral reactivation and that HCF-1 is rapidly recruited to the promoters of the viral IE genes upon initiation of reactivation. Data also suggests that HCF-1 modulates viral chromatin structure to initiate viral reactivation from latency. In 2015-2016, HCF complexes involved in viral reactivation from latency were isolated and identified. Additionally complexes that inhibit or drive HSV reactivation were studied. A mechanism involving histone modulation was identified that promotes HSV reactivation.

Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
Zip Code
Linehan, Jonathan L; Harrison, Oliver J; Han, Seong-Ji et al. (2018) Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue Repair. Cell 172:784-796.e18
Tallmadge, Rebecca L; Žygelyt?, Emilija; Van de Walle, Gerlinde R et al. (2018) Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 Activity In Vitro. Front Vet Sci 5:34
Sawant, Laximan; Kook, Insun; Vogel, Jodi L et al. (2018) The Cellular Coactivator HCF-1 Is Required for Glucocorticoid Receptor-Mediated Transcription of Bovine Herpesvirus 1 Immediate Early Genes. J Virol 92:
Alfonso-Dunn, Roberto; Turner, Anne-Marie W; Jean Beltran, Pierre M et al. (2017) Transcriptional Elongation of HSV Immediate Early Genes by the Super Elongation Complex Drives Lytic Infection and Reactivation from Latency. Cell Host Microbe 21:507-517.e5
Kristie, Thomas M (2015) Dynamic modulation of HSV chromatin drives initiation of infection and provides targets for epigenetic therapies. Virology 479-480:555-61
Cliffe, Anna R; Arbuckle, Jesse H; Vogel, Jodi L et al. (2015) Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation. Cell Host Microbe 18:649-58
Turner, Anne-Marie W; Arbuckle, Jesse H; Kristie, Thomas M (2014) Quantitative Analysis of HSV Gene Expression during Lytic Infection. Curr Protoc Microbiol 35:14E.5.1-27
Arbuckle, Jesse H; Kristie, Thomas M (2014) Epigenetic repression of herpes simplex virus infection by the nucleosome remodeler CHD3. MBio 5:e01027-13
Hill, James M; Quenelle, Debra C; Cardin, Rhonda D et al. (2014) Inhibition of LSD1 reduces herpesvirus infection, shedding, and recurrence by promoting epigenetic suppression of viral genomes. Sci Transl Med 6:265ra169
Americo, Jeffrey L; Sood, Cindy L; Cotter, Catherine A et al. (2014) Susceptibility of the wild-derived inbred CAST/Ei mouse to infection by orthopoxviruses analyzed by live bioluminescence imaging. Virology 449:120-32

Showing the most recent 10 out of 18 publications