Cloning, expression and characterization of ferret CXCL10.
Chemokines and their receptors function in the recruitment and activation of cells of the immune system to sites of inflammation. As such, chemokines play an important role in mediating pathophysiological events during microbial infection. In particular, CXCL9, CXCL10 and CXCL11 and their cognate receptor CXCR3 have been associated with the clinical course of several infectious diseases, including severe acute respiratory syndrome (SARS) and influenza. While CXCL9, CXCL10 and CXCL11 share the same receptor and have overlapping functions, each can also have unique activity in host defense. The lack of a preferred characterized animal model for SARS has brought our attention to ferrets, which have been used for years in influenza studies. The lack of immunological reagents for ferrets prompted us to clone CXCL9, CXCL10, CXCL11 and CXCR3 and, in the case of CXCL10, to express the gene as a recombinant protein. In this study we demonstrate that endogenous ferret CXCL10 exhibits similar mRNA expression patterns in the lungs of deceased SARS patients and ferrets experimentally infected with SARS coronavirus. This study therefore represents an important step towards development of the ferret as a model for the role of CXCL9, CXCL10 and CXCL11:CXCR3 axis in severe viral infections.
Danesh
Ali
A
Division of Experimental Therapeutics, Toronto General Research Institute, University Health Network, 101 College Street, Toronto, Ontario, Canada M5G 1L7.
Seneviratne
Charit
C
Cameron
Cheryl M
CM
Banner
David
D
Devries
Mark E
ME
Kelvin
Alyson A
AA
Xu
Luoling
L
Ran
Longsi
L
Bosinger
Steven E
SE
Rowe
Thomas
T
Czub
Marcus
M
Jonsson
Colleen B
CB
Cameron
Mark J
MJ
Kelvin
David J
DJ
D000818:Animals; D054357:Chemokine CXCL10 / Q000235:genetics*; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D003001:Cloning, Molecular; D005289:Ferrets; D005786:Gene Expression Regulation; D008297:Male; D023421:Models, Animal; D054367:Receptors, CXCR3; D045169:Severe Acute Respiratory Syndrome / Q000235:genetics
D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3