PMID- 24667863
OWN - NLM
STAT- MEDLINE
DCOM- 20140520
LR  - 20211021
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 55
IP  - 4
DP  - 2014 Apr 15
TI  - Overexpression of herpes simplex virus glycoprotein K (gK) alters expression of 
      HSV receptors in ocularly-infected mice.
PG  - 2442-51
LID - 10.1167/iovs.14-14013 [doi]
AB  - PURPOSE: We have shown previously that HSV-1 glycoprotein K (gK) exacerbates 
      corneal scarring (CS) in mice and rabbits. Here, we investigated the relative 
      impact of gK overexpression on host responses during primary corneal infection 
      and latency in trigeminal ganglia (TG) of infected mice. METHODS: Mice were 
      infected ocularly with HSV-gK(3) (expressing two extra copies of gK replacing 
      latency associated transcript [LAT]), HSV-gK(3) revertant (HSV-gK(3)R), or 
      wild-type HSV-1 strain McKrae. Individual corneas on day 5 post infection (PI) 
      and TG on day 28 PI were isolated and used for detection of gB DNA in the TG, 
      HSV-1 receptors in the cornea and TG, and inflammatory infiltrates in TG. 
      RESULTS: During primary HSV-1 infection, gK overexpression resulted in altered 
      expression of herpesvirus entry mediator (HVEM), 3-O-sulfated heparin sulfate 
      (3-OS-HS), paired immunoglobulin-like type 2 receptor-alpha (PILR-alpha), nectin-1, and 
      nectin-2 in cornea of BALB/c, but not C57BL/6 mice. However, gK overexpression 
      did have an effect on 3-OS-HS, PILR-alpha, nectin-1, and nectin-2 expression (but not 
      HVEM expression) in TG of C57BL/6 mice during latency. These differences did not 
      affect the level of latency, but instead were correlated with the presence of CS. 
      The presence of LAT increased HVEM expression and this effect was enhanced 
      further by the presence of CS in latently-infected mice. Finally, the presence of 
      LAT, but not overexpression of gK, affected CD4, CD8, TNF-alpha, Tim-3, PD-1, IL-21, 
      IL-2, and IFN-gamma expression in TG. CONCLUSIONS: We demonstrate a novel link 
      between gK exacerbation of CS and HSV-1 receptors, suggesting a gK-induced 
      molecular route for the pathogenesis as well as selective advantage of these 
      entry routes for the pathogen during latency-reactivation cycle.
FAU - Allen, Sariah J
AU  - Allen SJ
AD  - Center for Neurobiology and Vaccine Development, Ophthalmology Research, 
      Department of Surgery, Los Angeles, California, United States.
FAU - Mott, Kevin R
AU  - Mott KR
FAU - Ghiasi, Homayon
AU  - Ghiasi H
LA  - eng
GR  - R01 EY013615/EY/NEI NIH HHS/United States
GR  - 1 R01 EY13615/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140415
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (RNA, Viral)
RN  - 0 (Receptors, Virus)
RN  - 0 (UL53 protein, Human herpesvirus 1)
RN  - 0 (Viral Proteins)
RN  - 0 (simplexvirus receptor)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cornea/metabolism/pathology/*virology
MH  - Disease Models, Animal
MH  - Female
MH  - *Gene Expression Regulation
MH  - Herpesvirus 1, Human/genetics/*metabolism
MH  - Keratitis, Herpetic/genetics/*metabolism/virology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - RNA, Viral/*genetics
MH  - Rabbits
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Virus/biosynthesis/*genetics
MH  - Viral Proteins/biosynthesis/*genetics
MH  - Virus Replication
PMC - PMC3989088
OTO - NOTNLM
OT  - T cells
OT  - corneal scarring
OT  - cytokines
OT  - exhaustion
OT  - latency
OT  - virus replication
EDAT- 2014/03/29 06:00
MHDA- 2014/05/21 06:00
PMCR- 2014/10/01
CRDT- 2014/03/27 06:00
PHST- 2014/03/27 06:00 [entrez]
PHST- 2014/03/29 06:00 [pubmed]
PHST- 2014/05/21 06:00 [medline]
PHST- 2014/10/01 00:00 [pmc-release]
AID - iovs.14-14013 [pii]
AID - 10.1167/iovs.14-14013 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2014 Apr 15;55(4):2442-51. doi: 10.1167/iovs.14-14013.