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Journal of Virology, July 2006, p. 6339-6344, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00116-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Obligatory Requirement for Antibody in Recovery from a Primary Poxvirus Infection

Geeta Chaudhri,1 Vijay Panchanathan,1 Horst Bluethmann,2 and Gunasegaran Karupiah1*

Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, Australia,1 Roche Center for Medical Genomics, F. Hoffmann-La Roche, Basel, Switzerland2

Received 16 January 2006/ Accepted 21 April 2006

To understand the correlates of protective immunity against primary variola virus infection in humans, we have used the well-characterized mousepox model. This is an excellent surrogate small-animal model for smallpox in which the disease is caused by infection with the closely related orthopoxvirus, ectromelia virus. Similarities between the two infections include virus replication and transmission, aspects of pathology, and development of pock lesions. Previous studies using ectromelia virus have established critical roles for cytokines and effector functions of CD8 T cells in the control of acute stages of poxvirus infection. Here, we have used mice deficient in B cells to demonstrate that B-cell function is also obligatory for complete virus clearance and recovery of the host. In the absence of B cells, virus persists and the host succumbs to infection, despite the generation of CD8 T-cell responses. Intriguingly, transfer of naive B cells or ectromelia virus-immune serum to B-cell-deficient mice with established infection allowed these animals to clear virus and fully recover. In contrast, transfer of ectromelia virus-immune CD8 T cells was ineffective. Our data show that mice deficient in CD8 T-cell function die early in infection, whereas those deficient in B cells or antibody production die much later, indicating that B-cell function becomes critical after the effector phase of the CD8 T-cell response to infection subsides. Strikingly, our results show that antibody prevents virus from seeding the skin and forming pock lesions, which are important for virus transmission between hosts.


* Corresponding author. Mailing address: The John Curtin School of Medical Research, Building 54, Mills Road, Australian National University, Acton, ACT 0200, Australia. Phone: 61-2-6125-4562. Fax: 61-2-6125-2595. E-mail: guna.karupiah{at}anu.edu.au.


Journal of Virology, July 2006, p. 6339-6344, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00116-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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Copyright © 2006 by the American Society for Microbiology. All rights reserved.