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Journal of Virology, July 2006, p. 7245-7259, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00463-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Vaccinia Virus Activation of CCR5 Invokes Tyrosine Phosphorylation Signaling Events That Support Virus Replication

Ramtin Rahbar,1,2 Thomas T. Murooka,1,2 Anna A. Hinek,2 Carole L. Galligan,1 Antonella Sassano,3 Celeste Yu,2 Kishore Srivastava,3 Leonidas C. Platanias,3 and Eleanor N. Fish1,2*

Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2M1, Canada,1 Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada,2 Robert H. Lurie Cancer Center, Northwestern University School of Medicine, Chicago, Illinois 606113

Received 6 March 2006/ Accepted 26 April 2006

Vaccinia virus, a poxvirus, produces structurally distinct forms of virions for which the immediate events following cell entry are ill-defined. We provide evidence that intracellular mature virus (IMV) enters both permissive and nonpermissive T-cell lines and that introduction of CCR5 into nonpermissive mouse fibroblasts or human primary T cells renders the cells permissive for vaccinia replication. Notably, T cells expressing CCR5 in which tyrosine 339 in the intracellular region is replaced by phenylalanine no longer support virus replication or virus-inducible activation of specific host cell signaling effectors IRS-2, Grb2, and Erk1/2. We show that following IMV entry into the cell, the intact but not the tyrosine-deficient CCR5 is rapidly internalized and colocalizes with virus. This colocalization precedes virus-inducible signaling and replication.

* Corresponding author. Mailing address: Toronto General Research Institute, 67 College Street, Rm. 424, Toronto, Ontario M5G 2M1, Canada. Phone: (416) 340-5380. Fax: (416) 340-3453. E-mail: en.fish{at}utoronto.ca.

Journal of Virology, July 2006, p. 7245-7259, Vol. 80, No. 14
0022-538X/06/$08.00+0     doi:10.1128/JVI.00463-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Rahbar, R., Murooka, T. T., Fish, E. N. (2009). Role for CCR5 in Dissemination of Vaccinia Virus In Vivo. J. Virol. 83: 2226-2236 [Abstract] [Full Text]  
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