PMID- 20861248 OWN - NLM STAT- MEDLINE DCOM- 20101220 LR - 20211020 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 84 IP - 23 DP - 2010 Dec TI - Immunization with different viral antigens alters the pattern of T cell exhaustion and latency in herpes simplex virus type 1-infected mice. PG - 12315-24 LID - 10.1128/JVI.01600-10 [doi] AB - We have shown previously that immunization with herpes simplex virus type 1 (HSV-1) glycoprotein K (gK) exacerbated corneal scarring (CS) in ocularly infected mice. In this study, we investigated whether higher levels of CS were correlated with higher levels of latency and T cell exhaustion in gK-immunized mice. BALB/c mice were vaccinated with baculovirus-expressed gK or gD or mock immunized. Twenty-one days after the third immunization, mice were ocularly infected with 2 x 10(4) PFU/eye of virulent HSV-1 strain McKrae. On day 5 postinfection, virus replication in the eye was measured, and on day 30 postinfection, infiltration of the trigeminal ganglia (TG) by CD4, CD8, programmed death 1 (PD-1), and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was monitored by immunohistochemistry and quantitative real-time PCR (qRT-PCR). This study demonstrated that higher levels of CS were correlated with higher levels of latency, and this was associated with the presence of significantly higher numbers of CD4(+)PD-1(+) and CD8(+)PD-1(+) cells in the TG of the gK-immunized group than in both the gD- and mock-immunized groups. Levels of exhaustion associated with Tim-3 were the same among gK- and mock-vaccinated groups but higher than levels in the gD-vaccinated group. In this study, we have shown for the first time that both PD-1 and Tim-3 contribute to T cell exhaustion and an increase of latency in the TG of latently infected mice. FAU - Allen, Sariah J AU - Allen SJ AD - Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, Department of Surgery, CSMC Burns & Allen Research Institute, Los Angeles, California 90048, USA. FAU - Mott, Kevin R AU - Mott KR FAU - Zandian, Mandana AU - Zandian M FAU - Ghiasi, Homayon AU - Ghiasi H LA - eng GR - R01 EY013615/EY/NEI NIH HHS/United States GR - EY13615/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20100922 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antigens, Differentiation) RN - 0 (Antigens, Viral) RN - 0 (CD4 Antigens) RN - 0 (CD8 Antigens) RN - 0 (DNA Primers) RN - 0 (DNA, Complementary) RN - 0 (Havcr2 protein, mouse) RN - 0 (Hepatitis A Virus Cellular Receptor 2) RN - 0 (Pdcd1 protein, mouse) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Receptors, Virus) RN - 0 (UL53 protein, Human herpesvirus 1) RN - 0 (Viral Proteins) SB - IM MH - Analysis of Variance MH - Animals MH - Antigens, Differentiation/metabolism MH - Antigens, Viral/administration & dosage/*immunology MH - CD4 Antigens/metabolism MH - CD8 Antigens/metabolism MH - Cicatrix/pathology/*virology MH - Cornea/pathology/*virology MH - DNA Primers/genetics MH - DNA, Complementary/genetics MH - Hepatitis A Virus Cellular Receptor 2 MH - Herpes Simplex/*immunology/prevention & control MH - Herpesvirus 1, Human/genetics/*immunology/physiology MH - Immunization/*adverse effects MH - Immunohistochemistry MH - Mice MH - Mice, Inbred BALB C MH - Polymerase Chain Reaction MH - Programmed Cell Death 1 Receptor MH - Receptors, Virus/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Trigeminal Ganglion/metabolism MH - Viral Proteins/administration & dosage/*immunology MH - Virus Latency/*immunology MH - Virus Replication/physiology PMC - PMC2976415 EDAT- 2010/09/24 06:00 MHDA- 2010/12/21 06:00 PMCR- 2011/06/01 CRDT- 2010/09/24 06:00 PHST- 2010/09/24 06:00 [entrez] PHST- 2010/09/24 06:00 [pubmed] PHST- 2010/12/21 06:00 [medline] PHST- 2011/06/01 00:00 [pmc-release] AID - JVI.01600-10 [pii] AID - 1600-10 [pii] AID - 10.1128/JVI.01600-10 [doi] PST - ppublish SO - J Virol. 2010 Dec;84(23):12315-24. doi: 10.1128/JVI.01600-10. Epub 2010 Sep 22.