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Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses
BACKGROUND: Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) have caused widespread outbreaks of chronic polyarthritis. The inflammatory responses in alphavirus-induced arthritis and osteoarthritis (OA) share many similar features, which suggests the possibilit...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252017/ https://www.ncbi.nlm.nih.gov/pubmed/25407789 http://dx.doi.org/10.1186/s12985-014-0189-9 |
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author | Chen, Weiqiang Foo, Suan-Sin Li, Rachel W Smith, Paul N Mahalingam, Suresh |
author_facet | Chen, Weiqiang Foo, Suan-Sin Li, Rachel W Smith, Paul N Mahalingam, Suresh |
author_sort | Chen, Weiqiang |
collection | PubMed |
description | BACKGROUND: Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) have caused widespread outbreaks of chronic polyarthritis. The inflammatory responses in alphavirus-induced arthritis and osteoarthritis (OA) share many similar features, which suggests the possibility of exacerbated alphavirus-induced bone pathology in individuals with pre-existing OA. Here, we investigated the susceptibility of osteoblasts (OBs) from OA patients to RRV infection and dissected the immune mechanisms elicited from infection. METHODS: Primary hOBs obtained from trabecular bone of healthy donors and OA patients were infected with RRV. Infectivity and viral replication were determined using flow cytometry and plaque assay, respectively. Real-time PCR was performed to determine expression kinetics of type I interferon (IFN)-related immune mediators and osteotropic factors. RESULTS: OA hOBs showed enhanced RRV infectivity and replication during infection, which was associated with delayed induction of IFN-β and RIG-I expression. Enhanced susceptibility of OA hOBs to RRV was associated with a more pronounced increase in RANKL/OPG ratio and expression of osteotropic factors (IL-6, IL-1β, TNF-α and CCL2) in comparison to RRV-infected healthy hOBs. CONCLUSIONS: Delayed activation of type I IFN-signalling pathway may have contributed to enhanced susceptibility to RRV infection in hOBs from OA patients. RRV-induced increases in RANKL/OPG ratio and expression of osteotropic factors that favour bone resorption, which may be exacerbated during osteoarthritis. This study provides the novel insight that osteoarthritis may be a risk factor for exacerbated arthritogenic alphaviral infection. |
format | Online Article Text |
id | pubmed-4252017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42520172014-12-03 Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses Chen, Weiqiang Foo, Suan-Sin Li, Rachel W Smith, Paul N Mahalingam, Suresh Virol J Research BACKGROUND: Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) have caused widespread outbreaks of chronic polyarthritis. The inflammatory responses in alphavirus-induced arthritis and osteoarthritis (OA) share many similar features, which suggests the possibility of exacerbated alphavirus-induced bone pathology in individuals with pre-existing OA. Here, we investigated the susceptibility of osteoblasts (OBs) from OA patients to RRV infection and dissected the immune mechanisms elicited from infection. METHODS: Primary hOBs obtained from trabecular bone of healthy donors and OA patients were infected with RRV. Infectivity and viral replication were determined using flow cytometry and plaque assay, respectively. Real-time PCR was performed to determine expression kinetics of type I interferon (IFN)-related immune mediators and osteotropic factors. RESULTS: OA hOBs showed enhanced RRV infectivity and replication during infection, which was associated with delayed induction of IFN-β and RIG-I expression. Enhanced susceptibility of OA hOBs to RRV was associated with a more pronounced increase in RANKL/OPG ratio and expression of osteotropic factors (IL-6, IL-1β, TNF-α and CCL2) in comparison to RRV-infected healthy hOBs. CONCLUSIONS: Delayed activation of type I IFN-signalling pathway may have contributed to enhanced susceptibility to RRV infection in hOBs from OA patients. RRV-induced increases in RANKL/OPG ratio and expression of osteotropic factors that favour bone resorption, which may be exacerbated during osteoarthritis. This study provides the novel insight that osteoarthritis may be a risk factor for exacerbated arthritogenic alphaviral infection. BioMed Central 2014-11-19 /pmc/articles/PMC4252017/ /pubmed/25407789 http://dx.doi.org/10.1186/s12985-014-0189-9 Text en © Chen et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Chen, Weiqiang Foo, Suan-Sin Li, Rachel W Smith, Paul N Mahalingam, Suresh Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses |
title | Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses |
title_full | Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses |
title_fullStr | Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses |
title_full_unstemmed | Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses |
title_short | Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses |
title_sort | osteoblasts from osteoarthritis patients show enhanced susceptibility to ross river virus infection associated with delayed type i interferon responses |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252017/ https://www.ncbi.nlm.nih.gov/pubmed/25407789 http://dx.doi.org/10.1186/s12985-014-0189-9 |
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