PMID- 26962220
OWN - NLM
STAT- MEDLINE
DCOM- 20170426
LR  - 20220208
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 10
DP  - 2016 May 15
TI  - CD8+ T Cells Play a Bystander Role in Mice Latently Infected with Herpes Simplex 
      Virus 1.
PG  - 5059-5067
LID - 10.1128/JVI.00255-16 [doi]
AB  - Based on an explant reactivation model, it has been proposed that CD8(+) T cells 
      maintain latency in trigeminal ganglia (TG) of mice latently infected with herpes 
      simplex virus 1 (HSV-1) [T. Liu, K. M. Khanna, X. Chen, D. J. Fink, and R. L. 
      Hendricks, J Exp Med 191:1459-1466, 2000, doi:10.1084/jem.191.9.1459; K. M. 
      Khanna, R. H. Bonneau, P. R. Kinchington, and R. L. Hendricks, Immunity 
      18:593-603, 2003, doi:10.1016/S1074-7613(03)00112-2]. In those studies, BALB/c 
      mice were ocularly infected with an avirulent HSV-1 strain (RE) after corneal 
      scarification. However, in our studies, we typically infect mice with a virulent 
      HSV-1 strain (McKrae) that does not require corneal scarification. Using a 
      combination of knockout mice, adoptive transfers, and depletion studies, we 
      recently found that CD8alpha(+) dendritic cells (DCs) contribute to HSV-1 latency and 
      reactivation in TG of ocularly infected mice (K. R. Mott, S. J. Allen, M. 
      Zandian, B. Konda, B. G. Sharifi, C. Jones, S. L. Wechsler, T. Town, and H. 
      Ghiasi, PLoS One 9:e93444, 2014, doi:10.1371/journal.pone.0093444). This 
      suggested that CD8(+) T cells might not be the major regulators of HSV-1 latency 
      in the mouse TG. To investigate this iconoclastic possibility, we used a blocking 
      CD8 antibody and CD8(+) T cells in reactivated TG explants from mice latently 
      infected with (i) the avirulent HSV-1 strain RE following corneal scarification 
      or (ii) the virulent HSV-1 strain McKrae without corneal scarification. 
      Independently of the strain or approach, our results show that CD8alpha(+) DCs, not 
      CD8(+) T cells, drive latency and reactivation. In addition, adoptive transfer of 
      CD8(+) T cells from wild-type (wt) mice to CD8alpha(-/-) mice did not restore latency 
      to the level for wt mice or wt virus. In the presence of latency-associated 
      transcript (LAT((+)); wt virus), CD8(+) T cells seem to play a bystander role in 
      the TG. These bystander T cells highly express PD-1, most likely due to the 
      presence of CD8alpha(+) DCs. Collectively, these results support the notion that 
      CD8(+) T cells do not play a major role in maintaining HSV-1 latency and 
      reactivation. SIGNIFICANCE: This study addresses a fundamentally important and 
      widely debated issue in the field of HSV latency-reactivation. In this article, 
      we directly compare the effects of anti-CD8 antibody, CD8(+) T cells, LAT, and 
      CD8alpha(+) DCs in blocking explant reactivation in TG of mice latently infected with 
      avirulent or virulent HSV-1. Our data suggest that CD8(+) T cells are not 
      responsible for an increase or maintenance of latency in ocularly infected mice. 
      However, they seem to play a bystander role that correlates with the presence of 
      LAT, higher subclinical reactivation levels, and higher PD-1 expression levels.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Mott, Kevin R
AU  - Mott KR
AD  - Center for Neurobiology and Vaccine Development, Ophthalmology Research, 
      Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
FAU - Gate, David
AU  - Gate D
AD  - Zilkha Neurogenetic Institute, Department of Physiology & Biophysics, Keck School 
      of Medicine, University of Southern California, Los Angeles, California, USA.
FAU - Matundan, Harry H
AU  - Matundan HH
AD  - Center for Neurobiology and Vaccine Development, Ophthalmology Research, 
      Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
FAU - Ghiasi, Yasamin N
AU  - Ghiasi YN
AD  - Zilkha Neurogenetic Institute, Department of Physiology & Biophysics, Keck School 
      of Medicine, University of Southern California, Los Angeles, California, USA.
FAU - Town, Terrence
AU  - Town T
AD  - Zilkha Neurogenetic Institute, Department of Physiology & Biophysics, Keck School 
      of Medicine, University of Southern California, Los Angeles, California, USA.
FAU - Ghiasi, Homayon
AU  - Ghiasi H
AD  - Center for Neurobiology and Vaccine Development, Ophthalmology Research, 
      Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA 
      ghiasih@cshs.org.
LA  - eng
GR  - R01 EY014966/EY/NEI NIH HHS/United States
GR  - R01 EY024649/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160429
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Pdcd1 protein, mouse)
RN  - 0 (Programmed Cell Death 1 Receptor)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Dendritic Cells/chemistry/*immunology
MH  - Eye/virology
MH  - Herpesvirus 1, Human/*physiology
MH  - Keratitis, Herpetic/*immunology/*virology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Knockout
MH  - Programmed Cell Death 1 Receptor/genetics
MH  - Trigeminal Ganglion/*virology
MH  - Virus Activation
MH  - *Virus Latency
PMC - PMC4859724
EDAT- 2016/03/11 06:00
MHDA- 2017/04/27 06:00
PMCR- 2016/10/29
CRDT- 2016/03/11 06:00
PHST- 2016/02/09 00:00 [received]
PHST- 2016/03/01 00:00 [accepted]
PHST- 2016/03/11 06:00 [entrez]
PHST- 2016/03/11 06:00 [pubmed]
PHST- 2017/04/27 06:00 [medline]
PHST- 2016/10/29 00:00 [pmc-release]
AID - JVI.00255-16 [pii]
AID - 00255-16 [pii]
AID - 10.1128/JVI.00255-16 [doi]
PST - epublish
SO  - J Virol. 2016 Apr 29;90(10):5059-5067. doi: 10.1128/JVI.00255-16. Print 2016 May 
      15.