Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses
Autor(es): Chen Weiqiang, Foo Suan-Sin, Li Rachel W, Smith Paul N, Mahalingam Suresh
Resumo: Arthritogenic alphaviruses such as Ross River virus (RRV) - chikungunya virus (CHIKV) have caused widespread outbreaks of chronic polyarthritis. The inflammatory responses in alphavirus-induced arthritis - 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 - dissected the immune mechanisms elicited from infection. Primary hOBs obtained from trabecular bone of healthy donors - OA patients were infected with RRV. Infectivity - viral replication were determined using flow cytometry - plaque assay, respectively. Real-time PCR was performed to determine expression kinetics of type I interferon (IFN)-related immune mediators - osteotropic factors. OA hOBs showed enhanced RRV infectivity - replication during infection, which was associated with delayed induction of IFN-? - RIG-I expression. Enhanced susceptibility of OA hOBs to RRV was associated with a more pronounced increase in RANKL/OPG ratio - expression of osteotropic factors (IL-6, IL-1?, TNF-? - CCL2) in comparison to RRV-infected healthy hOBs. 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 - 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.
Palavras-Chave: Ross River virus; Human osteoblasts; RANKL/OPG ratio; Osteotropic factors
Imprenta: Virology Journal, v. 11, p. 189, 2014
Identificador do objeto digital: 10.1186/s12985-014-0189-9
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - Real Time PCR ; Chikungunya Virus - Virus ; Chikungunya virus - Immunology
Data de publicação: 2014
