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Generation of Induced-pluripotent Stem Cells Using Fibroblast-like Synoviocytes Isolated from Joints of Rheumatoid Arthritis Patients
Published on: October 16, 2016
Mayaro Virus Infects Human Chondrocytes and Induces the Expression of Arthritis-Related Genes Associated with Joint
Michèle Bengue1, Pauline Ferraris1, Cécile Baronti2
1MIVEGEC, IRD, Univ. Montpellier, CNRS, 34394 Montpellier, France.
Abstract:
Mayaro virus (MAYV) is an emerging arthritogenic alphavirus belonging to the Togaviridae family. Infection leads to a dengue-like illness accompanied by severe polyarthralgia. However, the molecular and cellular mechanisms of arthritis as a result of MAYV infection remain poorly understood. In the present study, we assess the susceptibility of human chondrocytes (HC), fibroblast-like synoviocytes and osteoblasts that are the major cell types involved in osteoarthritis, to infection with MAYV. We show that these cells are highly permissive to MAYV infection and that viral RNA copy number and viral titers increase over time in infected cells. Knowing that HC are the primary cells in articular cartilage and are essential for maintaining the cartilaginous matrix, gene expression studies were conducted in MAYV-infected primary HC using polymerase chain reaction (PCR) arrays. The infection of the latter cells resulted in an induction in the expression of several matrix metalloproteinases (MMP) including MMP1, MMP7, MMP8, MMP10, MMP13, MMP14 and MMP15 which could be involved in the destruction of articular cartilage. Infected HC were also found to express significantly increased levels of various IFN-stimulated genes and arthritogenic mediators such as TNF-α and IL-6. In conclusion, MAYV-infected primary HC overexpress arthritis-related genes, which may contribute to joint degradation and pathogenesis.
Insights
Mayaro virus (MAYV) infects human chondrocytes, leading to increased expression of matrix metalloproteinases and inflammatory mediators. This MAYV-induced gene expression may drive joint degradation and arthritis pathogenesis.
Area of Science:
- Virology
- Immunology
- Rheumatology
Background:
- Mayaro virus (MAYV) is an emerging alphavirus causing dengue-like illness with severe polyarthralgia.
- The mechanisms underlying MAYV-induced arthritis are not well understood.
Purpose of the Study:
- To investigate the susceptibility of human chondrocytes (HC), fibroblast-like synoviocytes, and osteoblasts to MAYV infection.
- To elucidate the molecular mechanisms of arthritis in MAYV infection.
Main Methods:
- Assessed MAYV permissiveness in human chondrocytes, synoviocytes, and osteoblasts.
- Quantified viral RNA and titers in infected cells.
- Utilized PCR arrays for gene expression analysis in MAYV-infected primary HC.
Main Results:
- Human chondrocytes, synoviocytes, and osteoblasts are highly permissive to MAYV.
- MAYV infection upregulated matrix metalloproteinases (MMPs) in HC, including MMP1, MMP7, MMP8, MMP10, MMP13, MMP14, and MMP15.
- Infected HC showed increased expression of IFN-stimulated genes, TNF-α, and IL-6.
Conclusions:
- MAYV-infected primary HC overexpress arthritis-related genes.
- This overexpression may contribute to articular cartilage degradation and the pathogenesis of MAYV-induced arthritis.
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