Abstract
Ectromelia virus (ECTV) is an orthopoxvirus (OPV) that causes mousepox, the murine equivalent of human smallpox. C57BL/6 (B6) mice are naturally resistant to mousepox due to the concerted action of innate and adaptive immune responses. Previous studies have shown that natural killer (NK) cells are a component of innate immunity that is essential for the B6 mice resistance to mousepox. However, the mechanism of NK cell–mediated resistance to OPV disease remains undefined. Here we show that B6 mice resistance to mousepox requires the direct cytolytic function of NK cells, as well as their ability to boost the T cell response. Furthermore, we show that the activating receptor NKG2D is required for optimal NK cell–mediated resistance to disease and lethality. Together, our results have important implication towards the understanding of natural resistance to pathogenic viral infections.
Highlights
Ectromelia virus (ECTV), the causative agent of mousepox, is an orthopoxvirus (OPV) with host specificity for the mouse
We show that Natural killer (NK) cells directly contribute to antiviral defenses by curbing virus dissemination to central organs and indirectly by augmenting the antiviral T cell response
Natural killer (NK) cells are cells of the innate immune system previously shown to play an important role in natural resistance to mousepox
Summary
Ectromelia virus (ECTV), the causative agent of mousepox, is an orthopoxvirus (OPV) with host specificity for the mouse. Mousepox is a severe disease with high mortality and infectivity. All mouse strains can be infected with ECTV, the outcome of the infection following footpad inoculation varies. Some sensitive strains, such as DBA/2, A/J, and BALB/c, develop mousepox and suffer high mortality during the first 2 wk post-infection, whereas other strains, such as C57BL/6 (B6), clear the infection without visible symptoms of systemic disease [5]. The resistance of B6 mice to mousepox is not due to an inherent decreased ability of the virus to replicate in this strain, but is a result of the combined action of the innate and adaptive immune systems [6,7,8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
