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ADAMTS5 is a critical regulator of virus-specific T cell immunity

McMahon, Meagan, Ye, Siying, Izzard, Leonard, Dlugolenski, Daniel, Tripp, Ralph A., Bean, Andrew G. D., McCulloch, Daniel R. and Stambas, John 2016, ADAMTS5 is a critical regulator of virus-specific T cell immunity, PLoS biology, vol. 14, no. 11, Article number : e1002580, pp. 1-22, doi: 10.1371/journal.pbio.1002580.

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Title ADAMTS5 is a critical regulator of virus-specific T cell immunity
Author(s) McMahon, Meagan
Ye, Siying
Izzard, Leonard
Dlugolenski, Daniel
Tripp, Ralph A.
Bean, Andrew G. D.
McCulloch, Daniel R.
Stambas, John
Journal name PLoS biology
Volume number 14
Issue number 11
Season Article number : e1002580
Start page 1
End page 22
Total pages 22
Publisher PLoS
Place of publication San Francisco, Calif.
Publication date 2016-11-17
ISSN 1544-9173
1545-7885
Summary The extracellular matrix (ECM) provides physical scaffolding for cellular constituents and initiates biochemical and biomechanical cues that are required for physiological activity of living tissues. The ECM enzyme ADAMTS5, a member of the ADAMTS (A Disintegrin-like and Metalloproteinase with Thrombospondin-1 motifs) protein family, cleaves large proteoglycans such as aggrecan, leading to the destruction of cartilage and osteoarthritis. However, its contribution to viral pathogenesis and immunity is currently undefined. Here, we use a combination of in vitro and in vivo models to show that ADAMTS5 enzymatic activity plays a key role in the development of influenza-specific immunity. Influenza virus infection of Adamts5-/- mice resulted in delayed virus clearance, compromised T cell migration and immunity and accumulation of versican, an ADAMTS5 proteoglycan substrate. Our research emphasises the importance of ADAMTS5 expression in the control of influenza virus infection and highlights the potential for development of ADAMTS5-based therapeutic strategies to reduce morbidity and mortality.
Language eng
DOI 10.1371/journal.pbio.1002580
Field of Research 110799 Immunology not elsewhere classified
Socio Economic Objective 920109 Infectious Diseases
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30091438

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.