Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production

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 multipli...

Full description

Bibliographic Details
Main Authors: Elisa X. Y. Lim, Aroon Supramaniam, Hayman Lui, Peta Coles, Wai Suet Lee, Xiang Liu, Penny A. Rudd, Lara J. Herrero
Format: Article
Language:English
Published: MDPI AG 2018-02-01
Series:Viruses
Subjects:
Online Access:http://www.mdpi.com/1999-4915/10/2/86
_version_ 1818991999971229696
author Elisa X. Y. Lim
Aroon Supramaniam
Hayman Lui
Peta Coles
Wai Suet Lee
Xiang Liu
Penny A. Rudd
Lara J. Herrero
author_facet Elisa X. Y. Lim
Aroon Supramaniam
Hayman Lui
Peta Coles
Wai Suet Lee
Xiang Liu
Penny A. Rudd
Lara J. Herrero
author_sort Elisa X. Y. Lim
collection DOAJ
description 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.
first_indexed 2024-12-20T20:19:12Z
format Article
id doaj.art-7ee38f3eb9b74599a86ebf0cad423d39
institution Directory Open Access Journal
issn 1999-4915
language English
last_indexed 2024-12-20T20:19:12Z
publishDate 2018-02-01
publisher MDPI AG
record_format Article
series Viruses
spelling doaj.art-7ee38f3eb9b74599a86ebf0cad423d392022-12-21T19:27:37ZengMDPI AGViruses1999-49152018-02-011028610.3390/v10020086v10020086Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor ProductionElisa X. Y. Lim0Aroon Supramaniam1Hayman Lui2Peta Coles3Wai Suet Lee4Xiang Liu5Penny A. Rudd6Lara J. Herrero7Institute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaInstitute for Glycomics, Griffith University, Gold Coast Campus, Southport, QLD 4215, AustraliaArthritogenic 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.http://www.mdpi.com/1999-4915/10/2/86cartilage degradationviral arthritisinflammatory disease
spellingShingle Elisa X. Y. Lim
Aroon Supramaniam
Hayman Lui
Peta Coles
Wai Suet Lee
Xiang Liu
Penny A. Rudd
Lara J. Herrero
Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production
Viruses
cartilage degradation
viral arthritis
inflammatory disease
title Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production
title_full Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production
title_fullStr Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production
title_full_unstemmed Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production
title_short Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production
title_sort chondrocytes contribute to alphaviral disease pathogenesis as a source of virus replication and soluble factor production
topic cartilage degradation
viral arthritis
inflammatory disease
url http://www.mdpi.com/1999-4915/10/2/86
work_keys_str_mv AT elisaxylim chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction
AT aroonsupramaniam chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction
AT haymanlui chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction
AT petacoles chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction
AT waisuetlee chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction
AT xiangliu chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction
AT pennyarudd chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction
AT larajherrero chondrocytescontributetoalphaviraldiseasepathogenesisasasourceofvirusreplicationandsolublefactorproduction