PMID- 33961904
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20220716
IS  - 1872-9096 (Electronic)
IS  - 0166-3542 (Print)
IS  - 0166-3542 (Linking)
VI  - 191
DP  - 2021 Jul
TI  - Wnt antagonists suppress herpes simplex virus type 1 productive infection.
PG  - 105082
LID - S0166-3542(21)00072-3 [pii]
LID - 10.1016/j.antiviral.2021.105082 [doi]
AB  - Following acute infection of mucosal surfaces, herpes simplex virus 1 (HSV-1) 
      establishes life-long latent infections within neurons, including sensory neurons 
      in trigeminal ganglia (TG). Periodically, reactivation from latency occurs 
      resulting in virus transmission and recurrent disease. In the absence of lytic 
      cycle viral transcriptional proteins, host factors are predicted to mediate early 
      stages of reactivation from latency. Previous studies suggested the canonical 
      Wnt/beta-catenin signaling pathway promotes productive infection. To further examine 
      how the Wnt/beta-catenin signaling pathway enhances productive infection, we 
      examined two antagonists of the Wnt-signaling pathway. KYA1797K enhances 
      formation of the beta-catenin destruction complex, resulting in beta-catenin 
      degradation. Conversely, iCRT14 inhibits beta-catenin dependent transcription by 
      interfering with beta-catenin interactions with T-cell factor/lymphoid enhancer 
      factor (TCF)/Lef family of cellular transcription factors and interferes with 
      TCF/Lef binding to DNA. iCRT14 and KYA1797K significantly inhibited HSV-1 
      productive infection in human and mouse neuronal cells and monkey kidney cells 
      (VERO). Although iCRT14 was only effective when present throughout infection, 
      delayed addition or early removal of KYA1797K did not significantly reduce its 
      antiviral properties. KYA1797K had no effect on virus entry or penetration 
      indicating it impairs certain aspects of viral replication. These studies 
      demonstrated beta-catenin promotes HSV-1 productive infection and indicate 
      antagonists of the canonical Wnt/beta-catenin signaling pathway may be effective 
      anti-HSV therapeutic agents.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Harrison, Kelly S
AU  - Harrison KS
AD  - Oklahoma State University, College of Veterinary Medicine, Department of 
      Veterinary Pathobiology, Stillwater, OK, 74078, USA.
FAU - Jones, Clinton
AU  - Jones C
AD  - Oklahoma State University, College of Veterinary Medicine, Department of 
      Veterinary Pathobiology, Stillwater, OK, 74078, USA. Electronic address: 
      clint.jones10@okstate.edu.
LA  - eng
GR  - P20 GM103648/GM/NIGMS NIH HHS/United States
GR  - R01 NS111167/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210505
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (Antiviral Agents)
RN  - 0 (KYA1797K)
RN  - 0 (Pyridines)
RN  - 0 (Pyrroles)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Thiazolidines)
RN  - 0 (beta Catenin)
RN  - 0 (iCRT14)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Cell Line, Tumor
MH  - Chlorocebus aethiops
MH  - Epithelial Cells/drug effects/virology
MH  - Herpesviridae Infections/drug therapy
MH  - Herpesvirus 1, Human/*drug effects
MH  - Humans
MH  - Pyridines/*pharmacology
MH  - Pyrroles/*pharmacology
MH  - Thiazolidinediones/*pharmacology
MH  - Thiazolidines/*pharmacology
MH  - Vero Cells
MH  - Virus Activation/drug effects
MH  - Virus Latency/*drug effects
MH  - Virus Replication/drug effects
MH  - *Wnt Signaling Pathway
MH  - beta Catenin/*antagonists & inhibitors
PMC - PMC8240022
MID - NIHMS1709434
COIS- Declaration of interests The authors declare that they have no known competing 
      financial interests or personal relationships that could have appeared to 
      influence the work reported in this paper. The authors declare the following 
      financial interests/personal relationships which may be considered as potential 
      competing interests: This manuscript is also not being considered for publication 
      in any other journal
EDAT- 2021/05/08 06:00
MHDA- 2021/12/15 06:00
PMCR- 2022/07/01
CRDT- 2021/05/07 20:20
PHST- 2021/02/12 00:00 [received]
PHST- 2021/04/23 00:00 [revised]
PHST- 2021/04/27 00:00 [accepted]
PHST- 2021/05/08 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/05/07 20:20 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - S0166-3542(21)00072-3 [pii]
AID - 10.1016/j.antiviral.2021.105082 [doi]
PST - ppublish
SO  - Antiviral Res. 2021 Jul;191:105082. doi: 10.1016/j.antiviral.2021.105082. Epub 
      2021 May 5.