Chikungunya Virus Infection Impairs the Function of Osteogenic Cells

ABSTRACT Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus spread by the Aedes species of mosquito. Chikungunya virus causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal the presence of bone lesions and erosive arthritis...

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Autores principales:	Enakshi Roy, Wen Shi, Bin Duan, St Patrick Reid
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Chikungunya virus mesenchymal stem cells osteogenic differentiation osteogenic cells Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b289a51a055f400dbebaa53ff11764b9
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spelling	oai:doaj.org-article:b289a51a055f400dbebaa53ff11764b92021-11-15T15:30:14ZChikungunya Virus Infection Impairs the Function of Osteogenic Cells10.1128/mSphere.00347-202379-5042https://doaj.org/article/b289a51a055f400dbebaa53ff11764b92020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00347-20https://doaj.org/toc/2379-5042ABSTRACT Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus spread by the Aedes species of mosquito. Chikungunya virus causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal the 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 leads 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. For the first time to our knowledge, we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed 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 the 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 that infection likely alters the function of osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.Enakshi RoyWen ShiBin DuanSt Patrick ReidAmerican Society for MicrobiologyarticleChikungunya virusmesenchymal stem cellsosteogenic differentiationosteogenic cellsMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chikungunya virus mesenchymal stem cells osteogenic differentiation osteogenic cells Microbiology QR1-502
spellingShingle	Chikungunya virus mesenchymal stem cells osteogenic differentiation osteogenic cells Microbiology QR1-502 Enakshi Roy Wen Shi Bin Duan St Patrick Reid Chikungunya Virus Infection Impairs the Function of Osteogenic Cells
description	ABSTRACT Chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus spread by the Aedes species of mosquito. Chikungunya virus causes a condition characterized by high fever, headache, rash, and joint pain. Recent investigations reveal the 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 leads 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. For the first time to our knowledge, we report that CHIKV can productively infect BMSCs and osteogenic cells. We also observed 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 the 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 that infection likely alters the function of osteogenic cells. This study highlights altered osteogenic differentiation as a possible mechanism for causing the bone pathology observed in CHIKV pathogenesis.
format	article
author	Enakshi Roy Wen Shi Bin Duan St Patrick Reid
author_facet	Enakshi Roy Wen Shi Bin Duan St Patrick Reid
author_sort	Enakshi Roy
title	Chikungunya Virus Infection Impairs the Function of Osteogenic Cells
title_short	Chikungunya Virus Infection Impairs the Function of Osteogenic Cells
title_full	Chikungunya Virus Infection Impairs the Function of Osteogenic Cells
title_fullStr	Chikungunya Virus Infection Impairs the Function of Osteogenic Cells
title_full_unstemmed	Chikungunya Virus Infection Impairs the Function of Osteogenic Cells
title_sort	chikungunya virus infection impairs the function of osteogenic cells
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/b289a51a055f400dbebaa53ff11764b9
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Chikungunya Virus Infection Impairs the Function of Osteogenic Cells

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