title: Osteoblasts from osteoarthritis patients show enhanced susceptibility to Ross River virus infection associated with delayed type I interferon responses.
abstract: 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.
authors.affiliation: Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, 4222, Australia. javier.chen@griffith.edu.au.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, 4222, Australia. j.foo@griffith.edu.au.
authors.forename: Suan-Sin
authors.initials: SS
authors.lastname: Foo
authors.affiliation: Trauma and Orthopaedic Research Unit Laboratory, The Medical School, The Australian National University, Garran Rd, Canberra, ACT 2601, Australia. Rachel.Li@anu.edu.au.
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Trauma and Orthopaedic Research Unit, The Canberra Hospital, Canberra, ACT 2605, Australia. psmith@orthoact.com.au.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Smith
authors.affiliation: Emerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast Campus, QLD, 4222, Australia. s.mahalingam@griffith.edu.au.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis; D010006:Osteoblasts / Q000276:immunology* / Q000821:virology*; D060888:Real-Time Polymerase Chain Reaction; D012398:Ross River virus / Q000254:growth & development / Q000502:physiology*; D010948:Viral Plaque Assay; D014779:Virus Replication
chemical_list: D007370:Interferon Type I