PMID- 35100323
OWN - NLM
STAT- MEDLINE
DCOM- 20220222
LR  - 20220222
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 18
IP  - 1
DP  - 2022 Jan
TI  - Absence of signal peptide peptidase in peripheral sensory neurons affects 
      latency-reactivation in HSV-1 ocularly infected mice.
PG  - e1010281
LID - 10.1371/journal.ppat.1010281 [doi]
LID - e1010281
AB  - We previously reported that HSV-1 infectivity in vitro and in vivo requires HSV 
      glycoprotein K (gK) binding to the ER signal peptide peptidase (SPP). 
      Anterograde-retrograde transport via peripheral nerves between the site of 
      infection (i.e., eye) and the site of latency (neurons) is a critical process to 
      establish latency and subsequent viral reactivation. Given the essential role of 
      neurons in HSV-1 latency-reactivation, we generated mice lacking SPP specifically 
      in peripheral sensory neurons by crossing Advillin-Cre mice with SPPfl/fl mice. 
      Expression of SPP mRNA and protein were significantly lower in neurons of 
      Avil-SPP-/- mice than in control mice despite similar levels of HSV-1 replication 
      in the eyes of Avil-SPP-/- mice and control mice. Viral transcript levels in 
      isolated neurons of infected mice on days 2 and 5 post infection were lower than 
      in control mice. Significantly less LAT, gB, and PD-1 expression was seen during 
      latency in isolated neurons and total trigeminal ganglia (TG) of Avil-SPP-/- mice 
      than in control mice. Finally, reduced latency and reduced T cell exhaustion in 
      infected Avil-SPP-/- mice correlated with slower and no reactivation. Overall, 
      our results suggest that blocking SPP expression in peripheral sensory neurons 
      does not affect primary virus replication or eye disease but does reduce 
      latency-reactivation. Thus, blocking of gK binding to SPP may be a useful tool to 
      reduce latency-reactivation.
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 - Tormanen, Kati
AU  - Tormanen K
AD  - Center for Neurobiology & Vaccine Development, Ophthalmology Research, Department 
      of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States 
      of America.
FAU - Hirose, Satoshi
AU  - Hirose S
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
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220131
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.- (signal peptide peptidase)
SB  - IM
MH  - Animals
MH  - Aspartic Acid Endopeptidases/*metabolism
MH  - Herpesvirus 1, Human
MH  - Keratitis, Herpetic/*virology
MH  - Mice
MH  - Sensory Receptor Cells/enzymology/*virology
MH  - Virus Activation/*physiology
MH  - Virus Latency/*physiology
MH  - Virus Replication/physiology
PMC - PMC8830783
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/02/01 06:00
MHDA- 2022/02/23 06:00
PMCR- 2022/01/31
CRDT- 2022/01/31 17:15
PHST- 2021/11/09 00:00 [received]
PHST- 2022/01/17 00:00 [accepted]
PHST- 2022/02/10 00:00 [revised]
PHST- 2022/02/01 06:00 [pubmed]
PHST- 2022/02/23 06:00 [medline]
PHST- 2022/01/31 17:15 [entrez]
PHST- 2022/01/31 00:00 [pmc-release]
AID - PPATHOGENS-D-21-02273 [pii]
AID - 10.1371/journal.ppat.1010281 [doi]
PST - epublish
SO  - PLoS Pathog. 2022 Jan 31;18(1):e1010281. doi: 10.1371/journal.ppat.1010281. 
      eCollection 2022 Jan.