Activation of COX-2/PGE2 promotes sapovirus replication via the inhibition of nitric oxide production

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Title
Activation of COX-2/PGE2 promotes sapovirus replication via the inhibition of nitric oxide production
Author(s)
M M Alfajaro; J S Choi; D S Kim; J Y Seo; J Y Kim; J G Park; M Soliman; Y B Baek; E H Cho; J Kwon; Hyung Jun KwonSu-Jin Park; Woo Song Lee; M I Kang; M Hosmillo; I Goodfellow; K O Cho
Bibliographic Citation
Journal of Virology, vol. 91, no. 3, pp. e01656-e01656
Publication Year
2017
Abstract
Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-L-methylarginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection.
Keyword
CalicivirusesCyclooxygenasesNitric oxideProstaglandin E2Sapovirus
ISSN
0022-538X
Publisher
Amer Soc Microb
DOI
http://dx.doi.org/10.1128/JVI.01656-16
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
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