Induction of natural killer cell responses by ectromelia virus controls infection. J Virol 2007 Apr;81(8):4070-9
Date
02/09/2007Pubmed ID
17287257Pubmed Central ID
PMC1866162DOI
10.1128/JVI.02061-06Scopus ID
2-s2.0-34247118409 (requires institutional sign-in at Scopus site) 93 CitationsAbstract
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 gammadelta 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.
Author List
Parker AK, Parker S, Yokoyama WM, Corbett JA, Buller RMAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cytotoxicity Tests, Immunologic
Disease Models, Animal
Ectromelia virus
Ectromelia, Infectious
Female
Flow Cytometry
Immunohistochemistry
Interferon-gamma
Killer Cells, Natural
Leukocyte Reduction Procedures
Liver
Mice
Mice, Inbred C57BL
Mice, Knockout
Spleen
Survival Analysis
