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1.
Am J Pathol ; 190(9): 1867-1880, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32479821

RESUMO

The most commonly reported symptom of post-Ebola virus disease syndrome in survivors is arthralgia, yet involvement of the joints in acute or convalescent Ebola virus infection is not well characterized in human patients or animal models. Through immunohistochemistry, we found that the lining synovial intima of the stifle (knee) is a target for acute infection by Ebola virus/Kikwit, Ebola virus/Makona-C05, and Marburg virus/Angola in the rhesus macaque model. Furthermore, histologic analysis, immunohistochemistry, RNAscope in situ hybridization, and transmission electron microscopy showed that synoviocytes of the stifle, shoulder, and hip are a target for mouse-adapted Ebola virus/Yambuku-Mayinga infection during acute disease in rhesus macaques. A time course of infection study with Ebola virus/Kikwit found that the large joint synovium became immunopositive beginning on postinfection day 6. In total, the synovium of 28 of 30 rhesus macaques with terminal filovirus disease had evidence of infection (64 of 96 joints examined). On the basis of immunofluorescence, infected cell types included CD68+ type A (macrophage-like) synoviocytes and CD44+ type B (fibroblast-like) synoviocytes. Cultured primary human fibroblast-like synoviocytes were permissive to infection with Ebola and Marburg viruses in vitro. Because synovial joints include immune privileged sites, these findings are significant for future investigations of filovirus pathogenesis and persistence as well as arthralgias in acute and convalescent filovirus disease.


Assuntos
Infecções por Filoviridae/virologia , Sinoviócitos/virologia , Animais , Células Cultivadas , Filoviridae , Humanos , Macaca mulatta
2.
J Gen Virol ; 99(4): 525-535, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29517478

RESUMO

Low-passage clinical isolates of chikungunya virus (CHIKV) were found to be a mixture of large- and small-plaque viruses, with small-plaque viruses being the predominant species. To investigate the contribution of plaque variants to the pathology of the joint, primary human fibroblast-like synoviocytes (HFLS) were used. Large- and small-plaque viruses were purified from two clinical isolates, CHIKV-031C and CHIKV-033C, and were designated CHIKV-031L and CHIKV-031S and CHIKV-033L and CHIKV-033S, respectively. The replication efficiencies of these viruses in HFLSs were compared and it was found that CHIKV-031S and CHIKV-033S replicated with the highest efficiency, while the parental clinical isolates had the lowest efficiency. Interestingly, the cytopathic effects (CPE) induced by these viruses correlated with neither the efficiency of replication nor the plaque size. The small-plaque viruses and the clinical isolates induced cell death rapidly, while large-plaque viruses induced slow CPE in which only 50 % of the cells in infected cultures were rounded up and detached on day 5 of infection. The production of proinflammatory cytokines and chemokines from infected HFLSs was evaluated. The results showed that the large-plaque viruses and the clinical isolates, but not small-plaque variants, were potent inducers of IL-6, IL-8 and MCP-1, and were able to migrate monocytes/macrophages efficiently. Sequencing data revealed a number of differences in amino acid sequences between the small- and large-plaque viruses. The results suggest that it is common for clinical isolates of CHIKV to be heterogeneous, while the variants may have distinct roles in the pathology of the joint.


Assuntos
Febre de Chikungunya/virologia , Vírus Chikungunya/fisiologia , Fibroblastos/virologia , Sinoviócitos/virologia , Células Cultivadas , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Febre de Chikungunya/genética , Febre de Chikungunya/imunologia , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Efeito Citopatogênico Viral , Fibroblastos/imunologia , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Sinoviócitos/imunologia
3.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39028255

RESUMO

Introduction. Ross River virus (RRV) is a mosquito-borne virus prevalent in Australia and the islands of the South Pacific, where it causes an arthritogenic illness with a hallmark feature of severe joint pain. The joint space is a unique microenvironment that contains cartilage and synovial fluid. Chondrocytes and synoviocytes are crucial components of the joint space and are known targets of RRV infection.Hypothesis/Gap statement. Understanding the relationship between synoviocytes and chondrocytes during RRV infection will provide further insights into RRV-induced joint pathology.Methodology. To better understand the unique dynamics of these cells during RRV infection, we used primary chondrocytes cultured in physiologically relevant micromasses. We then directly infected micromass chondrocytes or infected primary fibroblast-like synoviocytes (FLS), co-cultured with micromass chondrocytes. Micromass cultures and supernatants were collected and analysed for viral load with a PCR array of target genes known to play a role in arthritis.Results. We show that RRV through direct or secondary infection in micromass chondrocytes modulates the expression of cellular factors that likely contribute to joint inflammation and disease pathology, as well as symptoms such as pain. More importantly, while we show that RRV can infect micromass-cultured chondrocytes via FLS infection, FLS themselves affect the regulation of cellular genes known to contribute to arthritis.Conclusion. Single-cell culture systems lack the complexity of in vivo systems, and understanding the interaction between cell populations is crucial for deciphering disease pathology, including for the development of effective therapeutic strategies.


Assuntos
Condrócitos , Infecção por Ross River virus , Sinoviócitos , Humanos , Células Cultivadas , Condrócitos/virologia , Técnicas de Cocultura , Ross River virus , Infecção por Ross River virus/patologia , Infecção por Ross River virus/virologia , Sinoviócitos/virologia , Carga Viral
4.
Viruses ; 11(9)2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470617

RESUMO

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.


Assuntos
Infecções por Alphavirus/virologia , Alphavirus/fisiologia , Artrite/genética , Condrócitos/virologia , Alphavirus/imunologia , Infecções por Alphavirus/genética , Infecções por Alphavirus/imunologia , Adesão Celular/genética , Sobrevivência Celular , Células Cultivadas , Condrócitos/imunologia , Citocinas/genética , Citocinas/metabolismo , Matriz Extracelular/genética , Perfilação da Expressão Gênica , Humanos , Metaloproteinases da Matriz/genética , Osteoblastos/virologia , RNA Viral/metabolismo , Sinoviócitos/virologia
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