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Journal of Virology, November 2008, p. 11263-11272, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01352-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Complement Receptor 3 Promotes Severe Ross River Virus-Induced Disease{triangledown}

Thomas E. Morrison,1,3 Jason D. Simmons,2,3 and Mark T. Heise1,2,3*

Department of Genetics,1 Department of Microbiology and Immunology,2 Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 275993

Received 27 June 2008/ Accepted 28 August 2008

Alphaviruses such as Ross River virus (RRV) and chikungunya virus are mosquito-transmitted viruses that cause explosive epidemics of debilitating arthritis and myositis affecting millions of humans worldwide. Previous studies using a mouse model of RRV-induced disease demonstrated that viral infection results in a severe inflammatory arthritis and myositis and that complement component 3 (C3) contributes to the destructive phase of the inflammatory disease but not the recruitment of cellular infiltrates to the sites of RRV-induced inflammation. Here, we demonstrate that mice deficient in complement receptor 3 (CR3) (CD11b–/–), a signaling receptor activated by multiple ligands including the C3 cleavage fragment iC3b, develop less-severe disease signs and decreased tissue destruction compared to RRV-infected wild-type mice. CR3 deficiency had no effect on viral replication, nor did it diminish the magnitude, kinetics, and composition of the cellular infiltrates at the sites of inflammation. However, the genetic absence of CR3 diminished the expression of specific proinflammatory and cytotoxic effectors, including S100A9/S100A8 and interleukin-6, within the inflamed tissues, suggesting that CR3-dependent signaling at the sites of inflammation contributes to tissue damage and severe disease.

* Corresponding author. Mailing address: The Carolina Vaccine Institute, University of North Carolina at Chapel Hill, 9024 Burnett Womack, CB #7292, Manning Drive, Chapel Hill, NC 27599. Phone: (919) 843-1492. Fax: (919) 843-6924. E-mail: heisem{at}med.unc.edu

{triangledown} Published ahead of print on 10 September 2008.

Journal of Virology, November 2008, p. 11263-11272, Vol. 82, No. 22
0022-538X/08/$08.00+0     doi:10.1128/JVI.01352-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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