Why the study?
Chondrocytes are thought to play a vital role in Ross River virus disease pathogenesis and cartilage degradation, but their pathways and transcriptomes during infection remained to be examined.
RRV-infected and bystander chondrocytes exhibit both shared and unique transcriptomic signatures, highlighting the need for careful selection of therapeutic targets to minimize adverse effects on uninfected cells.
Demands selective antiviral targets to spare bystander chondrocytes; leaves open translation from this animal model to human disease.
Old world alphaviruses, such as Ross River virus (RRV), cause debilitating arthralgia during acute and chronic stages of the disease. RRV-induced cartilage degradation has been implicated as a cause of joint pain felt by RRV patients. Chondrocytes are a major cell type of cartilage and are involved in the production and maintenance of the cartilage matrix. It is thought that these cells may play a vital role in RRV disease pathogenesis. In this study, we used RNA-sequencing (RNA-Seq) to examine the transcriptomes of RRV-infected and bystander chondrocytes in the same environment. RRV containing green fluorescent protein (GFP) allowed for the separation of RRV-infected (GFP+) and bystander uninfected cells (GFP−). We found that whereas GFP+ and GFP− populations commonly presented similar gene expression profiles during infection, there were also unique signatures. For example, RIMS2 and FOXJ1 were unique to GFP+ cells, whilst Aim2 and CCL8 were only found in bystander chondrocytes. This indicates that careful selection of potential therapeutic targets is important to minimise adverse effects to the neighbouring uninfected cell populations. Our study serves as a resource to provide more information about the pathways and responses elicited by RRV in cells which are both infected and stimulated because of neighbouring infected cells.
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Lim et al. (2022) studied this question.
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