Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses

Virology Journal

Suresh Mahalingam³  Paul N Smith²  Rachel W Li¹  Suan-Sin Foo³  Weiqiang Chen³ 

[1] Trauma and Orthopaedic Research Unit Laboratory, The Medical School, The Australian National University, Garran Rd, Canberra ACT 2601, Australia;Department of Orthopaedic Surgery, Trauma and Orthopaedic Research Unit, The Canberra Hospital, Canberra ACT 2605, Australia;Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast Campus 4222, QLD, Australia

关键词: Osteotropic factors;    RANKL/OPG ratio;    Human osteoblasts;    Ross River virus;   

Others  :  1148134
DOI  :  10.1186/s12985-014-0189-9

 received in 2014-07-17, accepted in 2014-10-26,  发布年份 2014

【 摘 要 】

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-? 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-1?, TNF-? 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.

【 授权许可】

   
2014 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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