PMID- 19846508 OWN - NLM STAT- MEDLINE DCOM- 20100121 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 84 IP - 1 DP - 2010 Jan TI - 17-beta estradiol promotion of herpes simplex virus type 1 reactivation is estrogen receptor dependent. PG - 565-72 LID - 10.1128/JVI.01374-09 [doi] AB - Correlations between estrogen and herpes simplex virus (HSV) reactivation from latency have been suggested by numerous clinical reports, but causal associations are not well delineated. In a murine HSV-1 corneal infection model, we establish 17-beta estradiol (17-betaE) treatment of latently infected ovariectomized mice induces viral reactivation, as demonstrated by increased viral load and increased immediate-early viral gene expression in the latently infected trigeminal ganglia (TG). Interestingly, the increased HSV reactivation occurred in the absence of inhibition of viral specific CD8(+) T-cell effector function. 17-betaE administration increased HSV reactivation in CD45(+) cell-depleted TG explant cultures, providing further support that leukocyte-independent effects on latently infected neurons were responsible for the increased reactivation. The drug-induced increases in HSV copy number were not recapitulated upon in vivo treatment of latently infected estrogen receptor alpha-deficient mice, evidence that HSV reactivation promoted by 17-betaE was estrogen receptor dependent. These findings provide additional framework for the emerging conceptualization of HSV latency as a dynamic process maintained by complex interactions among multiple cooperative and competing host, viral, and environmental forces. Additional research is needed to confirm whether pregnancy or hormonal contraceptives containing 17-betaE also promote HSV reactivation from latency in an estrogen receptor-dependent manner. FAU - Vicetti Miguel, Rodolfo D AU - Vicetti Miguel RD AD - Graduate Program in Immunology, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. [corrected]. FAU - Sheridan, Brian S AU - Sheridan BS FAU - Harvey, Stephen A K AU - Harvey SA FAU - Schreiner, Robert S AU - Schreiner RS FAU - Hendricks, Robert L AU - Hendricks RL FAU - Cherpes, Thomas L AU - Cherpes TL LA - eng GR - T32 AI060525/AI/NIAID NIH HHS/United States GR - P30EY08098/EY/NEI NIH HHS/United States GR - R01 EY005945/EY/NEI NIH HHS/United States GR - T32 AI 060525/AI/NIAID NIH HHS/United States GR - P30 EY008098/EY/NEI NIH HHS/United States GR - K23 AI064396/AI/NIAID NIH HHS/United States GR - R01 EY05945/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Estrogen Receptor alpha) RN - 0 (Receptors, Estrogen) RN - 4TI98Z838E (Estradiol) SB - IM EIN - J Virol. 2012 Aug;86(16):8917 MH - Animals MH - Corneal Diseases/virology MH - *Estradiol MH - Estrogen Receptor alpha/deficiency/*physiology MH - Eye Infections, Viral MH - Female MH - Genes, Immediate-Early MH - Herpesvirus 1, Human/*physiology MH - Mice MH - Mice, Knockout MH - *Receptors, Estrogen MH - Viral Load MH - *Virus Activation MH - Virus Latency PMC - PMC2798450 EDAT- 2009/10/23 06:00 MHDA- 2010/01/22 06:00 PMCR- 2010/07/01 CRDT- 2009/10/23 06:00 PHST- 2009/10/23 06:00 [entrez] PHST- 2009/10/23 06:00 [pubmed] PHST- 2010/01/22 06:00 [medline] PHST- 2010/07/01 00:00 [pmc-release] AID - JVI.01374-09 [pii] AID - 1374-09 [pii] AID - 10.1128/JVI.01374-09 [doi] PST - ppublish SO - J Virol. 2010 Jan;84(1):565-72. doi: 10.1128/JVI.01374-09.