PMID- 31167920
OWN - NLM
STAT- MEDLINE
DCOM- 20200603
LR  - 20200603
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 93
IP  - 16
DP  - 2019 Aug 15
TI  - CD28 Costimulation Is Required for Development of Herpetic Stromal Keratitis but 
      Does Not Prevent Establishment of Latency.
LID - 10.1128/JVI.00659-19 [doi]
LID - e00659-19
AB  - Corneal infection with herpes simplex virus 1 (HSV-1) leads to infection of 
      trigeminal ganglia (TG), typically followed by the establishment of latency in 
      the infected neurons. When latency is disrupted, the virus reactivates and 
      migrates back to the cornea, where it restimulates the immune response, leading 
      to lesions in a disease called herpetic stromal keratitis (HSK). HSK requires T 
      cell activation, as in the absence of T cells there is no disease. We decided to 
      determine if CD28 costimulation of T cells was required in HSK. The results 
      indicated that C57BL/6 CD28(-/-) and BALB/c CD28(-/-) mice failed to develop 
      recurrent HSK, while their wild-type counterparts did. In order to better 
      understand the dynamics of TG infection in these mice, we evaluated the amount of 
      virus in infected TG and the number of individual neurons harboring latent virus. 
      The results indicated that CD28(-/-) mice possessed significantly increased 
      genome levels in their TG but many fewer LAT-positive cells than wild-type mice 
      from day 7 to day 30 but that after day 30 these differences became 
      nonsignificant. We next evaluated total and antigen-specific CD8(+) T cells in 
      TG. The results indicated that there were significantly fewer CD8 T cells in TG 
      from day 10 to day 25 but that after that the differences were not significant. 
      Taken together, these data suggest that CD28 costimulation is required for HSK 
      but that while initial infection of TG is greater in CD28(-/-) mice, this begins 
      to normalize with time and this normalization is concurrent with the delayed 
      development of antigen-specific CD8(+) T cells.IMPORTANCE We study the 
      pathogenesis of herpes simplex virus-mediated corneal disease. T cells play a 
      critical role both in disease and in the maintenance of latency in neurons. 
      Consequently, the focus of this study was to evaluate the role that T cell 
      costimulation plays both in corneal disease and in controlling the ability of the 
      virus to maintain a stable infection of the ganglia that innervate the cornea. We 
      demonstrate that in the absence of costimulation with CD28, corneal disease does 
      not take place. However, this costimulation does not prevent the ability of 
      CD8(+) T cells to develop and, thus, control latent infection of neurons. We 
      conclude from these studies that CD28 costimulation is required for corneal 
      destructive immune responses but that CD8(+) T cells develop over time and help 
      to maintain latency.
CI  - Copyright (c) 2019 American Society for Microbiology.
FAU - Yin, Xiao-Tang
AU  - Yin XT
AD  - Department of Ophthalmology, Saint Louis University School of Medicine, St. 
      Louis, Missouri, USA.
FAU - Baugnon, Nicholas K
AU  - Baugnon NK
AD  - Department of Ophthalmology, Saint Louis University School of Medicine, St. 
      Louis, Missouri, USA.
FAU - Potter, Chloe A
AU  - Potter CA
AD  - Department of Ophthalmology, Saint Louis University School of Medicine, St. 
      Louis, Missouri, USA.
FAU - Tai, Shannon
AU  - Tai S
AD  - Department of Ophthalmology, Saint Louis University School of Medicine, St. 
      Louis, Missouri, USA.
FAU - Keadle, Tammie L
AU  - Keadle TL
AD  - Department of Ophthalmology, Saint Louis University School of Medicine, St. 
      Louis, Missouri, USA.
FAU - Stuart, Patrick M
AU  - Stuart PM
AD  - Department of Ophthalmology, Saint Louis University School of Medicine, St. 
      Louis, Missouri, USA pstuart2@slu.edu.
LA  - eng
GR  - R01 EY016352/EY/NEI NIH HHS/United States
GR  - R01 EY021247/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190730
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CD28 Antigens)
SB  - IM
MH  - Animals
MH  - CD28 Antigens/*metabolism
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism
MH  - Disease Models, Animal
MH  - *Disease Susceptibility
MH  - Herpesvirus 1, Human/*physiology
MH  - *Host-Pathogen Interactions
MH  - Keratitis, Herpetic/*metabolism/*virology
MH  - Mice
MH  - Mice, Knockout
MH  - *Virus Latency
MH  - Virus Shedding
PMC - PMC6675882
OTO - NOTNLM
OT  - T cell costimulation
OT  - ocular immunology
OT  - viral pathogenesis
EDAT- 2019/06/07 06:00
MHDA- 2020/06/04 06:00
PMCR- 2020/01/30
CRDT- 2019/06/07 06:00
PHST- 2019/04/19 00:00 [received]
PHST- 2019/05/31 00:00 [accepted]
PHST- 2019/06/07 06:00 [pubmed]
PHST- 2020/06/04 06:00 [medline]
PHST- 2019/06/07 06:00 [entrez]
PHST- 2020/01/30 00:00 [pmc-release]
AID - JVI.00659-19 [pii]
AID - 00659-19 [pii]
AID - 10.1128/JVI.00659-19 [doi]
PST - epublish
SO  - J Virol. 2019 Jul 30;93(16):e00659-19. doi: 10.1128/JVI.00659-19. Print 2019 Aug 
      15.