Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.

Cyclooxygenases (COXs)/prostaglandin E2 (PGE2) signaling pathways are known to modulate a variety of homeostatic processes and are involved in various pathophysiological conditions. COXs/PGE2 signaling pathways have also been demonstrated to have proviral or antiviral effects, which appeared differe...

Full description

Bibliographic Details
Main Authors: Mia Madel Alfajaro, Eun-Hyo Cho, Jun-Gyu Park, Ji-Yun Kim, Mahmoud Soliman, Yeong-Bin Baek, Mun-Il Kang, Sang-Ik Park, Kyoung-Oh Cho
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC6051663?pdf=render
_version_ 1818847137370210304
author Mia Madel Alfajaro
Eun-Hyo Cho
Jun-Gyu Park
Ji-Yun Kim
Mahmoud Soliman
Yeong-Bin Baek
Mun-Il Kang
Sang-Ik Park
Kyoung-Oh Cho
author_facet Mia Madel Alfajaro
Eun-Hyo Cho
Jun-Gyu Park
Ji-Yun Kim
Mahmoud Soliman
Yeong-Bin Baek
Mun-Il Kang
Sang-Ik Park
Kyoung-Oh Cho
author_sort Mia Madel Alfajaro
collection DOAJ
description Cyclooxygenases (COXs)/prostaglandin E2 (PGE2) signaling pathways are known to modulate a variety of homeostatic processes and are involved in various pathophysiological conditions. COXs/PGE2 signaling pathways have also been demonstrated to have proviral or antiviral effects, which appeared different even in the same virus family. A porcine sapovirus Cowden strain, a member of genus Sapovirus within the Caliciviridae family, induces strong COX-2/PGE2 but transient COX-1/PGE2 signaling to enhance virus replication. However, whether infections of other viruses in the different genera activate COXs/PGE2 signaling, and thus affect the replication of viruses, remains unknown. In the present study, infections of cells with the feline calicivirus (FCV) F9 strain in the genus Vesivirus and murine norovirus (MNV) CW-1 strain in the genus Norovirus only activated the COX-2/PGE2 signaling in a time-dependent manner. Treatment with pharmacological inhibitors or transfection of small interfering RNAs (siRNAs) against COX-2 enzyme significantly reduced the production of PGE2 as well as FCV and MNV replications. The inhibitory effects of these pharmacological inhibitors against COX-2 enzyme on the replication of both viruses were restored by the addition of PGE2. Silencing of COX-1 via siRNAs and inhibition of COX-1 via an inhibitor also decrease the production of PGE2 and replication of both viruses, which can be attributed to the inhibition COX-1/PGE2 signaling pathway. These data indicate that the COX-2/PGE2 signaling pathway has proviral effects for the replication of FCV and MNV, and pharmacological inhibitors against these enzymes serve as potential therapeutic candidates for treating FCV and MNV infections.
first_indexed 2024-12-19T05:56:40Z
format Article
id doaj.art-4e3411025ad648149a7ca67c83c4c42f
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-19T05:56:40Z
publishDate 2018-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-4e3411025ad648149a7ca67c83c4c42f2022-12-21T20:33:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01137e020072610.1371/journal.pone.0200726Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.Mia Madel AlfajaroEun-Hyo ChoJun-Gyu ParkJi-Yun KimMahmoud SolimanYeong-Bin BaekMun-Il KangSang-Ik ParkKyoung-Oh ChoCyclooxygenases (COXs)/prostaglandin E2 (PGE2) signaling pathways are known to modulate a variety of homeostatic processes and are involved in various pathophysiological conditions. COXs/PGE2 signaling pathways have also been demonstrated to have proviral or antiviral effects, which appeared different even in the same virus family. A porcine sapovirus Cowden strain, a member of genus Sapovirus within the Caliciviridae family, induces strong COX-2/PGE2 but transient COX-1/PGE2 signaling to enhance virus replication. However, whether infections of other viruses in the different genera activate COXs/PGE2 signaling, and thus affect the replication of viruses, remains unknown. In the present study, infections of cells with the feline calicivirus (FCV) F9 strain in the genus Vesivirus and murine norovirus (MNV) CW-1 strain in the genus Norovirus only activated the COX-2/PGE2 signaling in a time-dependent manner. Treatment with pharmacological inhibitors or transfection of small interfering RNAs (siRNAs) against COX-2 enzyme significantly reduced the production of PGE2 as well as FCV and MNV replications. The inhibitory effects of these pharmacological inhibitors against COX-2 enzyme on the replication of both viruses were restored by the addition of PGE2. Silencing of COX-1 via siRNAs and inhibition of COX-1 via an inhibitor also decrease the production of PGE2 and replication of both viruses, which can be attributed to the inhibition COX-1/PGE2 signaling pathway. These data indicate that the COX-2/PGE2 signaling pathway has proviral effects for the replication of FCV and MNV, and pharmacological inhibitors against these enzymes serve as potential therapeutic candidates for treating FCV and MNV infections.http://europepmc.org/articles/PMC6051663?pdf=render
spellingShingle Mia Madel Alfajaro
Eun-Hyo Cho
Jun-Gyu Park
Ji-Yun Kim
Mahmoud Soliman
Yeong-Bin Baek
Mun-Il Kang
Sang-Ik Park
Kyoung-Oh Cho
Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.
PLoS ONE
title Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.
title_full Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.
title_fullStr Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.
title_full_unstemmed Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.
title_short Feline calicivirus- and murine norovirus-induced COX-2/PGE2 signaling pathway has proviral effects.
title_sort feline calicivirus and murine norovirus induced cox 2 pge2 signaling pathway has proviral effects
url http://europepmc.org/articles/PMC6051663?pdf=render
work_keys_str_mv AT miamadelalfajaro felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT eunhyocho felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT jungyupark felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT jiyunkim felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT mahmoudsoliman felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT yeongbinbaek felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT munilkang felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT sangikpark felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects
AT kyoungohcho felinecalicivirusandmurinenorovirusinducedcox2pge2signalingpathwayhasproviraleffects