The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact

• Published in: iScience Vol. 25; no. 12; p. 105510
• Main Authors: Peauroi, Elise M., Carro, Stephen D., Pei, Luxin, Reynoso, Glennys V., Hickman, Heather D., Eisenlohr, Laurence C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22-12-2022; Elsevier
• Subjects: Components of the immune system; Immunology; Virology; Components of the immune system; Immunology; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105510

The success of poxviruses as pathogens depends on their antagonism of host responses by multiple immunomodulatory proteins. The largest of these expressed by ectromelia virus (the agent of mousepox) is C15, one member of a well-conserved poxviral family previously shown to inhibit T cell activation. Here, we demonstrate by quantitative immunofluorescence imaging that C15 also limits contact between natural killer (NK) cells and infected cells in vivo. This corresponds to an inhibition in the number of total and degranulating NK cells, ex vivo and in vitro, with no detectable impact on NK cell cytokine production or the transcription of factors related to NK cell recruitment or activation. Thus, in addition to its previously identified capacity to antagonize CD4 T cell activation, C15 inhibits NK cell cytolytic function, which results in increased viral replication and dissemination in vivo. This work builds on a body of literature demonstrating the importance of early restriction of virus within the draining lymph node.
[Display omitted]
•Ectromelia virus C15 protein facilitates early viral replication and dissemination•Early effect of ECTV C15 dependent on NK cells•ECTV C15 inhibits NK cell number and cytolytic function•ECTV C15 limits contact between NK cells and infected cells in vivo
Components of the immune system; Immunology; Virology