PMID- 36215312
OWN - NLM
STAT- MEDLINE
DCOM- 20221024
LR  - 20221024
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 18
IP  - 10
DP  - 2022 Oct
TI  - Knockout of signal peptide peptidase in the eye reduces HSV-1 replication and eye 
      disease in ocularly infected mice.
PG  - e1010898
LID - 10.1371/journal.ppat.1010898 [doi]
LID - e1010898
AB  - We previously reported that knocking out signal peptide peptidase (SPP), a 
      glycoprotein K (gK) binding partner, in mouse peripheral sensory neurons reduced 
      latency-reactivation in infected mice without affecting primary virus replication 
      or eye disease. Since virus replication in the eye plays an essential role in eye 
      disease, we generated a conditional knockout mouse lacking SPP expression in the 
      eye by crossing Pax6 (paired box 6)-Cre mice that have intact Pax6 expression 
      with SPPflox/flox mice. Significantly less SPP protein expression was detected in 
      the eyes of Pax6-SPP-/- mice than in WT control mice. HSV-1 replication in the 
      eyes of Pax6-SPP-/- mice was significantly lower than in WT control mice. Levels 
      of gB, gK, and ICP0 transcripts in corneas, but not trigeminal ganglia (TG), of 
      Pax6-SPP-/- infected mice were also significantly lower than in WT mice. Corneal 
      scarring and angiogenesis were significantly lower in Pax6-SPP-/- mice than in WT 
      control mice, while corneal sensitivity was significantly higher in Pax6-SPP-/- 
      mice compared with WT control mice. During acute viral infection, absence of SPP 
      in the eye did not affect CD4 expression but did affect CD8alpha and IFNgamma expression 
      in the eye. However, in the absence of SPP, latency-reactivation was similar in 
      Pax6-SPP-/- and WT control groups. Overall, our results showed that deleting SPP 
      expression in the eyes reduced primary virus replication in the eyes, reduced 
      CD8alpha and IFNgamma mRNA expression, reduced eye disease and reduced angiogenesis but 
      did not alter corneal sensitivity or latency reactivation to HSV-1 infection. 
      Thus, blocking gK binding to SPP in the eye may have therapeutic potential by 
      reducing both virus replication in the eye and eye disease associated with virus 
      replication.
FAU - Wang, Shaohui
AU  - Wang S
AD  - Center for Neurobiology & Vaccine Development, Ophthalmology Research, Department 
      of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States 
      of America.
FAU - Jaggi, Ujjaldeep
AU  - Jaggi U
AD  - Center for Neurobiology & Vaccine Development, Ophthalmology Research, Department 
      of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States 
      of America.
FAU - Ghiasi, Homayon
AU  - Ghiasi H
AUID- ORCID: 0000-0003-3291-1995
AD  - Center for Neurobiology & Vaccine Development, Ophthalmology Research, Department 
      of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States 
      of America.
LA  - eng
GR  - R01 EY013615/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 - 20221010
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - EC 3.4.23.- (signal peptide peptidase)
RN  - 0 (RNA, Messenger)
RN  - 0 (Glycoproteins)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Herpesvirus 1, Human/physiology
MH  - *Keratitis, Herpetic/genetics
MH  - Mice, Knockout
MH  - *Herpes Simplex/genetics
MH  - Trigeminal Ganglion
MH  - *Eye Diseases
MH  - Virus Replication/physiology
MH  - Cornea
MH  - RNA, Messenger
MH  - Glycoproteins
MH  - Virus Latency/physiology
MH  - Mice, Inbred BALB C
PMC - PMC9584536
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/10/11 06:00
MHDA- 2022/10/25 06:00
PMCR- 2022/10/10
CRDT- 2022/10/10 13:53
PHST- 2022/08/08 00:00 [received]
PHST- 2022/09/26 00:00 [accepted]
PHST- 2022/10/20 00:00 [revised]
PHST- 2022/10/11 06:00 [pubmed]
PHST- 2022/10/25 06:00 [medline]
PHST- 2022/10/10 13:53 [entrez]
PHST- 2022/10/10 00:00 [pmc-release]
AID - PPATHOGENS-D-22-01384 [pii]
AID - 10.1371/journal.ppat.1010898 [doi]
PST - epublish
SO  - PLoS Pathog. 2022 Oct 10;18(10):e1010898. doi: 10.1371/journal.ppat.1010898. 
      eCollection 2022 Oct.