title: ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity.
abstract: 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.
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Meagan
authors.initials: M
authors.lastname: McMahon
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Siying
authors.initials: S
authors.lastname: Ye
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Leonard
authors.initials: L
authors.lastname: Izzard
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dlugolenski
authors.affiliation: College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
authors.affiliation: Australian Animal Health Laboratory, CSIRO, East Geelong, Victoria, Australia.
authors.forename: Andrew G D
authors.identifier: http://orcid.org/0000-0002-4585-3811
authors.initials: AG
authors.lastname: Bean
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: Daniel R
authors.identifier: http://orcid.org/0000-0003-0269-5857
authors.initials: DR
authors.lastname: McCulloch
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Stambas
mesh_terms: D000071116:ADAMTS5 Protein / Q000235:genetics / Q000502:physiology*; D000818:Animals; D007111:Immunity, Cellular / Q000502:physiology*; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D053675:Versicans / Q000378:metabolism; D015431:Weight Loss
chemical_list: D053675:Versicans; D000071116:ADAMTS5 Protein; C498489:Adamts5 protein, mouse