Chikungunya virus (CHIKV) is an alphavirus, transmitted by mosquitoes, which causes Chikungunya fever with symptoms of fever, rash, headache, and joint pain. In about 30%–40% of cases, the infection leads to polyarthritis and polyarthralgia. Presently, there are no treatment strategies or vaccine for Chikungunya fever. Moreover, the mechanism of CHIKV induced bone pathology is not fully understood. The modulation of host machinery is known to be essential in establishing viral pathogenesis. MicroRNAs (miRNAs) are small non-coding RNAs that regulate major cellular functions by modulating gene expression. Fascinatingly, recent reports have indicated the role of miRNAs in regulating bone homeostasis and altered expression of miRNAs in bone-related pathological diseases. In this review, we summarize the altered expression of miRNAs during CHIKV pathogenesis and the possible role of miRNAs during bone homeostasis in the context of CHIKV infection. A holistic understanding of the different signaling pathways targeted by miRNAs during bone remodeling and during CHIKV-induced bone pathology may lead to identification of useful biomarkers or therapeutics.

Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus, spread by the Aedes species (sp.) mosquitoes. Chikungunya virus (CHIKV) causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal presence of bone lesions and erosive arthritis in the joints of CHIKV infected patients, indicating an association of bone pathology with CHIKV infection. However, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Bone marrow derived mesenchymal stem cells (BMSCs) contribute to bone homeostasis by differentiating into osteogenic cells which later mature to form the bone. Disruption of osteogenic differentiation and function of BMSCs lead to bone pathologies. Studies show that virus infections can alter the properties and function of BMSCs. However, to date, pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMSCs and osteogenic cells to CHIKV and studied the effect of infection on these cells. To our knowledge, for the first time we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed a decreased gene expression of the major regulator of osteogenic differentiation, RUNX2 in CHIKV infected osteogenic cells. Furthermore, impaired functional properties of osteogenic cells i.e. decreased production and activity of alkaline phosphatase (ALP) and matrix mineralization were observed in the presence of CHIKV infection. Thus, we conclude that CHIKV likely impairs osteogenic differentiation of BMSCs indicating a possible role of BMSCs in altering bone homeostasis during CHIKV infection. Importance: Presently, no vaccines or treatment options are available for CHIKV infection. Joint pain is one of the major concerns. Although studies have shown an association between bone pathology and infection, the molecular pathogenesis in context of bone pathology is poorly defined. Here, we demonstrate for the first time that BMSCs and BMSC-derived osteogenic cells are susceptible to CHIKV infection and infection likely alters function of the osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.

Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus, belonging to the genus alphavirus in the family Togaviridae . The virus is spread by the Aedes species (sp.) mosquitoes in tropical and subtropical regions of the world. CHIKV causes Chikungunya fever (CHIKF), where the acute stage of infection is characterized by high fever, headache, rash, and polyarthralgia. In 30-40% of cases, patients develop a chronic stage with debilitating joint pain persisting for months to years imposing a burden on the population in terms of disability adjusted life years (DALY). Presently, no vaccines or treatment options are available for this infection. Prior investigations reveal that CHIKV infection is associated with bone pathology; however, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Studies show that disruption of osteogenic differentiation and function of bone marrow-derived mesenchymal stem cells (BMMSCs) can lead to bone pathologies. However, to date pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMMSCs to CHIKV and studied the effect of infection on BMMSCs-derived osteogenic cells. To our knowledge, for the first time we report that CHIKV can productively infect BMMSCs. We observed a decrease in the intracellular and extracellular alkaline phosphatase (ALP) activity and reduction in calcium phosphate deposition in infected cells compared to mock-infected control. Thus, we conclude that CHIKV infects BMMSCs and disrupts function of osteogenic cells. Importance: Although studies have shown association of bone pathology and CHIKV infection, the pathogenesis of infection causing altered bone homeostasis is not fully understood. Here, we demonstrate for the first time that BMMSCs are susceptible to CHIKV infection. Furthermore, we observe that infection causes disruption in the function of BMMSC- derived osteogenic cells. Impaired function of these osteogenic cells will likely lead to a disruption in bone homeostasis and in part, provides a mechanism for the observed bone pathology associated with CHIKV pathogenesis.