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Journal of Virology, April 2007, p. 4070-4079, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02061-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Induction of Natural Killer Cell Responses by Ectromelia Virus Controls Infection{triangledown}

April Keim Parker,1 Scott Parker,1 Wayne M. Yokoyama,2 John A. Corbett,1,3 and R. Mark L. Buller1*

Departments of Molecular Microbiology and Immunology,1 Biochemistry and Molecular Biology, Saint Louis University Health Sciences Center, 1402 South Grand Blvd., Saint Louis, Missouri 63104,3 Howard Hughes Medical Institute, Rheumatology Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 631102

Received 20 September 2006/ Accepted 31 January 2007

Natural killer (NK) cells play a pivotal role in the innate immune response to viral infections, particularly murine cytomegalovirus (MCMV) and human herpesviruses. In poxvirus infections, the role of NK cells is less clear. We examined disease progression in C57BL/6 mice after the removal of NK cells by both antibody depletion and genetic means. We found that NK cells were crucial for survival and the early control of virus replication in spleen and to a lesser extent in liver in C57BL/6 mice. Studies of various knockout mice suggested that {gamma}{delta} T cells and NKT cells are not important in the C57BL/6 mousepox model and CD4+ and CD8+ T cells do not exhibit antiviral activity at 6 days postinfection, when the absence of NK cells has a profound effect on virus titers in spleen and liver. NK cell cytotoxicity and/or gamma interferon (IFN-{gamma}) secretion likely mediated the antiviral effect needed to control virus infectivity in target organs. Studies of the effects of ectromelia virus (ECTV) infection on NK cells demonstrated that NK cells proliferate within target tissues (spleen and liver) and become activated following a low-dose footpad infection, although the mechanism of activation appears distinct from the ligand-dependent activation observed with MCMV. NK cell IFN-{gamma} secretion was detected by intracellular cytokine staining transiently at 32 to 72 h postinfection in the lymph node, suggesting a role in establishing a Th1 response. These results confirm a crucial role for NK cells in controlling an ECTV infection.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, 1402 South Grand Blvd., St. Louis, MO 63104. Phone: (314) 977-8870. Fax: (314) 977-8717. E-mail: bullerrm{at}slu.edu

{triangledown} Published ahead of print on 7 February 2007.

Journal of Virology, April 2007, p. 4070-4079, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02061-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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