Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation
The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We...
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| Veröffentlicht in: | PLoS pathogens 2015-02, Vol.11 (2), p.e1004649-e1004649 |
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| creator | Foo, Suan-Sin Chen, Weiqiang Taylor, Adam Sheng, Kuo-Ching Yu, Xing Teng, Terk-Shin Reading, Patrick C Blanchard, Helen Garlanda, Cecilia Mantovani, Alberto Ng, Lisa F P Herrero, Lara J Mahalingam, Suresh |
| description | The rising prevalence of arthritogenic alphavirus infections, including chikungunya virus (CHIKV) and Ross River virus (RRV), and the lack of antiviral treatments highlight the potential threat of a global alphavirus pandemic. The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis. |
| doi_str_mv | 10.1371/journal.ppat.1004649 |
| format | Article |
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The immune responses underlying alphavirus virulence remain enigmatic. We found that pentraxin 3 (PTX3) was highly expressed in CHIKV and RRV patients during acute disease. Overt expression of PTX3 in CHIKV patients was associated with increased viral load and disease severity. PTX3-deficient (PTX3(-/-)) mice acutely infected with RRV exhibited delayed disease progression and rapid recovery through diminished inflammatory responses and viral replication. Furthermore, binding of the N-terminal domain of PTX3 to RRV facilitated viral entry and replication. Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1004649</identifier><identifier>PMID: 25695775</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alphavirus Infections - immunology ; Animals ; Arthritis ; C-Reactive Protein - immunology ; Cells, Cultured ; Disease ; Enzyme-Linked Immunosorbent Assay ; Experiments ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Genetic aspects ; Health aspects ; Host-virus relationships ; Humans ; Identification and classification ; Infections ; Male ; Medical research ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins - immunology ; Pathogenesis ; Real-Time Polymerase Chain Reaction ; RNA viruses ; Scholarships & fellowships ; Serum Amyloid P-Component - immunology ; Transcriptome ; Transfection ; Tumor necrosis factor-TNF ; Viral Load - immunology ; Viral proteins ; Virus replication ; Virus Replication - immunology</subject><ispartof>PLoS pathogens, 2015-02, Vol.11 (2), p.e1004649-e1004649</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Foo et al 2015 Foo et al</rights><rights>2015 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Foo S-S, Chen W, Taylor A, Sheng K-C, Yu X, Teng T-S, et al. (2015) Role of Pentraxin 3 in Shaping Arthritogenic Alphaviral Disease: From Enhanced Viral Replication to Immunomodulation. 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Thus, our study demonstrates the pivotal role of PTX3 in shaping alphavirus-triggered immunity and disease and provides new insights into alphavirus pathogenesis.</description><subject>Alphavirus Infections - immunology</subject><subject>Animals</subject><subject>Arthritis</subject><subject>C-Reactive Protein - immunology</subject><subject>Cells, Cultured</subject><subject>Disease</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Experiments</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Host-virus relationships</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Infections</subject><subject>Male</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nerve Tissue Proteins - immunology</subject><subject>Pathogenesis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>RNA viruses</subject><subject>Scholarships & fellowships</subject><subject>Serum Amyloid P-Component - immunology</subject><subject>Transcriptome</subject><subject>Transfection</subject><subject>Tumor necrosis factor-TNF</subject><subject>Viral Load - immunology</subject><subject>Viral proteins</subject><subject>Virus replication</subject><subject>Virus Replication - immunology</subject><issn>1553-7374</issn><issn>1553-7366</issn><issn>1553-7374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVkl1rFTEQhhdRbK3-A9GAN3pxjptNstn1QijFjwNFoep1mJPM7knJJmuyW-q_N-ejpQe8kUASZp55M7yZonhJyyVlkr6_DnP04JbjCNOSliWvefuoOKVCsIVkkj9-cD8pnqV0nRnKaP20OKlE3QopxWkxXQWHJHRkRD9FuLWeMJK3tIHR-p5AnDbRTqFHbzUBN27gxkZwxNiEkPAD6WIYCPoNeI2G7JMRR2c1TDZ4MgVih2H2YQhmdrvY8-JJBy7hi8N5Vvz6_OnnxdfF5fcvq4vzy4WuGZsWneQa16KBWjcMqamqddei4LSjrEJelhSgkiAaw7gpeYs15wYk69aVRIQ1Oyte73VHF5I6GJYUrZu2kTWreSZWe8IEuFZjtAPEPyqAVbtAiL3KDljtUNUNa4zhVdu2hjeCtVBVQuR-WqgFIMtaHw-vzesBjd4Z6o5EjzPeblQfbhRnTJRyK_D2IBDD7xnTpAabNDoHHsO87VtIVpUVKzP6Zo_2kFuzvgtZUW9xdc5pwzjjtM7U8h9UXgYHq4PHzub4UcG7o4LMTHg79TCnpFY_rv6D_XbM8j2rY0gpYnfvCi3VdprvPkdtp1kdpjmXvXro6H3R3fiyv1D58nA</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Foo, Suan-Sin</creator><creator>Chen, Weiqiang</creator><creator>Taylor, Adam</creator><creator>Sheng, Kuo-Ching</creator><creator>Yu, Xing</creator><creator>Teng, Terk-Shin</creator><creator>Reading, Patrick C</creator><creator>Blanchard, Helen</creator><creator>Garlanda, Cecilia</creator><creator>Mantovani, Alberto</creator><creator>Ng, Lisa F P</creator><creator>Herrero, Lara J</creator><creator>Mahalingam, Suresh</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150201</creationdate><title>Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation</title><author>Foo, Suan-Sin ; 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| subjects | Alphavirus Infections - immunology Animals Arthritis C-Reactive Protein - immunology Cells, Cultured Disease Enzyme-Linked Immunosorbent Assay Experiments Female Flow Cytometry Fluorescent Antibody Technique Genetic aspects Health aspects Host-virus relationships Humans Identification and classification Infections Male Medical research Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins - immunology Pathogenesis Real-Time Polymerase Chain Reaction RNA viruses Scholarships & fellowships Serum Amyloid P-Component - immunology Transcriptome Transfection Tumor necrosis factor-TNF Viral Load - immunology Viral proteins Virus replication Virus Replication - immunology |
| title | Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation |
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