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Journal of Virology, March 2009, p. 2226-2236, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.01655-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role for CCR5 in Dissemination of Vaccinia Virus In Vivo{triangledown}

Ramtin Rahbar, Thomas T. Murooka, and Eleanor N. Fish*

Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2M1, Canada, and Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Received 4 August 2008/ Accepted 4 December 2008

In an earlier report, we provided evidence that expression of CCR5 by primary human T cells renders them permissive for vaccinia virus (VACV) replication. This may represent a mechanism for dissemination throughout the lymphatic system. To test this hypothesis, wild-type CCR5+/+ and CCR5 null mice were challenged with VACV by intranasal inoculation. In time course studies using different infective doses of VACV, we identified viral replication in the lungs of both CCR5+/+ and CCR5–/– mice, yet there were diminished viral loads in the spleens and brains of CCR5–/– mice compared with CCR5+/+ mice. Moreover, in association with VACV infection, we provide evidence for CD4+ and CD8+ T-cell as well as CD11c+ and F4/80+ cell infiltration into the lungs of CCR5+/+ but not CCR5–/– mice, and we show that the CCR5-expressing T cells harbor virus. We demonstrate that this CCR5 dependence is VACV specific, since CCR5–/– mice are as susceptible to intranasal influenza virus (A/WSN/33) infection as CCR5+/+ mice. In a final series of experiments, we provide evidence that adoptive transfer of CCR5+/+ bone marrow leukocytes into CCR5–/– mice restores VACV permissiveness, with evidence of lung and spleen infection. Taken together, our data suggest a novel role for CCR5 in VACV dissemination in vivo.

* 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

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

Journal of Virology, March 2009, p. 2226-2236, Vol. 83, No. 5
0022-538X/09/$08.00+0     doi:10.1128/JVI.01655-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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