| Autor: |
Shmeleva EV; Department of Pathology, University of Cambridge, Cambridge, UK.; Present address: Department of Biology, Tufts University, Medford, Massachusetts, USA., Syafiq D; Department of Pathology, University of Cambridge, Cambridge, UK.; Present address: Gonville and Caius College, University of Cambridge, Cambridge, UK., Moldoveanu AL; Department of Pathology, University of Cambridge, Cambridge, UK.; Present address: Section of Microbiology, Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, UK., Ferguson BJ; Department of Pathology, University of Cambridge, Cambridge, UK., Smith GL; Department of Pathology, University of Cambridge, Cambridge, UK. |
| Abstrakt: |
Vaccinia virus (VACV) protein N1 is an intracellular immunomodulator that contributes to virus virulence via inhibition of NF-κB. Intradermal infection with a VACV lacking gene N1L (vΔN1) results in smaller skin lesions than infection with wild-type virus (WT VACV), but the impact of N1 deletion on the local microbiota as well as the innate and cellular immune responses in infected ear tissue is mostly uncharacterized. Here, we analysed the bacterial burden and host immune response at the site of infection and report that the presence of protein N1 correlated with enhanced expansion of skin microbiota, even before lesion development. Furthermore, early after infection (days 1-3), prior to lesion development, the levels of inflammatory mediators were higher in vΔN1-infected tissue compared to WT VACV infection. In contrast, infiltration of ear tissue with myeloid and lymphoid cells was greater after WT VACV infection and there was significantly greater secondary bacterial infection that correlated with greater lesion size. We conclude that a more robust innate immune response to vΔN1 infection leads to better control of virus replication, less bacterial growth and hence an overall reduction of tissue damage and lesion size. This analysis shows the potent impact of a single viral immunomodulator on the host immune response and the pathophysiology of VACV infection in the skin. |
