Abstract
Arthritogenic alphavirus infections often result in debilitating musculoskeletal disorders that affect the joints, muscle, and bone. In order to evaluate the infection profile of primary human skeletal muscle and chondrocyte cells to Ross River virus (RRV) in vitro, cells were infected at a multiplicity of infection (MOI) of 1 over a period of two days. Viral titers were determined by plaque assay and cytokine expression by Bio-Plex® assays using the supernatants harvested. Gene expression studies were conducted using total RNA isolated from cells. Firstly, we show that RRV RNA is detected in chondrocytes from infected mice in vivo. Both human primary skeletal muscle and chondrocyte cells are able to support productive RRV infection in vitro. We also report the production of soluble host factors including the upregulation of heparanase (HPSE) and inflammatory host factors such as interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation, normal T cell expressed and secreted), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α), which are also present during clinical disease in humans. Our study is the first to demonstrate that human chondrocyte cells are permissive to RRV infection, support the production of infectious virus, and produce soluble factors including HPSE, which may contribute to joint degradation and the pathogenesis of disease.
Highlights
The occurrence of rheumatic manifestations in viral diseases, mimicking those seen in degenerative osteoarthritis (OA) or autoimmune rheumatic arthritis (RA), is not an unfamiliar concept [1,2]
River virus (RRV)-positive chondrocytes were observed within the ankle joints of infected mice
There are sporadic reports showing that chondrocytes are susceptible to virus infections and play an important role in the related disease pathogenesis
Summary
The occurrence of rheumatic manifestations in viral diseases, mimicking those seen in degenerative osteoarthritis (OA) or autoimmune rheumatic arthritis (RA), is not an unfamiliar concept [1,2]. Arthritogenic alphaviral diseases (such as Ross River virus; RRV and chikungunya virus; CHIKV) have been described to have comparable clinical symptoms as well as both joint damage and inflammatory factor profiles as with those found in both OA and RA. As reported in studies on the pathogenesis of OA, the expression of certain pro-inflammatory cytokines (interleukin-6; IL-6 and interleukin 1 beta; IL-1β) determines the degree of cartilage degeneration. These soluble mediators are heavily upregulated in arthritogenic alphaviral disease, suggesting similar disease pathophysiology [3,4]. Human arthritogenic alphavirus infection results in a range of clinical manifestations, both acute and chronic phases of disease.
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