PMID- 19091870 OWN - NLM STAT- MEDLINE DCOM- 20090216 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 83 IP - 5 DP - 2009 Mar TI - Level of herpes simplex virus type 1 latency correlates with severity of corneal scarring and exhaustion of CD8+ T cells in trigeminal ganglia of latently infected mice. PG - 2246-54 LID - 10.1128/JVI.02234-08 [doi] AB - A hallmark of infection with herpes simplex virus type 1 (HSV-1) is the establishment of latency in ganglia of the infected individual. During the life of the latently infected individual, the virus can occasionally reactivate, travel back to the eye, and cause recurrent disease. Indeed, a major cause of corneal scarring (CS) is the scarring induced by HSV-1 following reactivation from latency. In this study, we evaluated the relationship between the amount of CS and the level of the HSV-1 latency-associated transcript (LAT) in trigeminal ganglia (TG) of latently infected mice. Our results suggested that the amount of CS was not related to the amount of virus replication following primary ocular HSV-1 infection, since replication in the eyes was similar in mice that did not develop CS, mice that developed CS in just one eye, and mice that developed CS in both eyes. In contrast, mice with no CS had significantly less LAT, and thus presumably less latency, in their TG than mice that had CS in both eyes. Higher CS also correlated with higher levels of mRNAs for PD-1, CD4, CD8, F4/80, interleukin-4, gamma interferon, granzyme A, and granzyme B in both cornea and TG. These results suggest that (i) the immunopathology induced by HSV-1 infection does not correlate with primary virus replication in the eye; (ii) increased CS appears to correlate with increased latency in the TG, although the possible cause-and-effect relationship is not known; and (iii) increased latency in mouse TG correlates with higher levels of PD-1 mRNA, suggesting exhaustion of CD8+ T cells. FAU - Mott, Kevin R AU - Mott KR AD - Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, CSMC Burns & Allen Research Institute, Los Angeles, California 90048, USA. FAU - Bresee, Catherine J AU - Bresee CJ FAU - Allen, Sariah J AU - Allen SJ FAU - BenMohamed, Lbachir AU - BenMohamed L FAU - Wechsler, Steven L AU - Wechsler SL FAU - Ghiasi, Homayon AU - Ghiasi H LA - eng GR - R01 EY013615/EY/NEI NIH HHS/United States GR - R01 EY014966/EY/NEI NIH HHS/United States GR - EY13615/EY/NEI NIH HHS/United States GR - EY14966/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20081217 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antigens, Surface) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (MicroRNAs) RN - 0 (Pdcd1 protein, mouse) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (latency associated transcript, herpes simplex virus-1) SB - IM MH - Animals MH - Antigens, Surface/genetics/metabolism MH - Apoptosis Regulatory Proteins/genetics/metabolism MH - CD8-Positive T-Lymphocytes/metabolism/*pathology/virology MH - Cornea/*pathology/virology MH - Corneal Diseases/virology MH - Female MH - Herpes Simplex/*pathology MH - Herpesvirus 1, Human/genetics/*pathogenicity/physiology MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/genetics/metabolism MH - Programmed Cell Death 1 Receptor MH - Trigeminal Ganglion/immunology/*virology MH - Virus Activation MH - *Virus Latency PMC - PMC2643740 EDAT- 2008/12/19 09:00 MHDA- 2009/02/17 09:00 PMCR- 2009/09/01 CRDT- 2008/12/19 09:00 PHST- 2008/12/19 09:00 [entrez] PHST- 2008/12/19 09:00 [pubmed] PHST- 2009/02/17 09:00 [medline] PHST- 2009/09/01 00:00 [pmc-release] AID - JVI.02234-08 [pii] AID - 2234-08 [pii] AID - 10.1128/JVI.02234-08 [doi] PST - ppublish SO - J Virol. 2009 Mar;83(5):2246-54. doi: 10.1128/JVI.02234-08. Epub 2008 Dec 17.