Detalle de: Ectromelia NF-κβ inhibitor 002 is essential for virus pathogenesis (154.4)

Ectromelia virus is an orthopoxvirus and the causative agent of mousepox in mice. The virus codifies several proteins to control the host response. One of them is the NF-κβ inhibitor, ECTV 002 which has orthologs in other poxviruses including cowpox, monkeypox and variola viruses. We generated an ectromelia virus that lacks this gene (ECTV Δ002) and its correspondent revertant virus. Both viruses grew normally in vitro; however, when used to infected BALB/C mice in the footpad, only the WT and revertant viruses killed the mice. When using different doses, the LD50s were lower than 1pfu for the WT and revertant viruses but higher than 105 for the ECTV Δ002 indicating an attenuation of at least 5 orders of magnitude. We then analyzed the virus spread by measuring virus titers in different organs. The virus load in the draining lymph node was lower in mice infected with the ECTV Δ002 than with the revertant virus and consequently, the virus titer in peripheral organs like spleen or liver was lower as well. When we compared the immune responses in the draining lymph nodes by flow cytometry, we did not find significant differences between ECTV Δ002 and WT viruses. However, 7 dpi, the mice infected with ECTV Δ002 had elevated numbers of NK, CD8 and CD4 cells in their spleens as compared to mice infected with revertant virus. Altogether our results show that ECTV 002 is essential for ECTV pathogenesis and that the control of the infection occurs early in the draining lymph node.