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Volume 103, Issue 11

Suppression of innate immunity by the vaccinia virus protein N1 promotes skin microbiota expansion and increased immune infiltration following vaccination Open Access

Abstract

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 (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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): innate immunity , N1 , NF-κB , skin microbiota and Vaccinia virus
Funding
This study was supported by the:
  • Wellcome Trust (Award 090315)
    • Principle Award Recipient: GeoffreyL. Smith
  • Medical Research Council (Award MR/M019810/1)
    • Principle Award Recipient: SmithGeoffrey L.FergusonBrian J.
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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/content/journal/jgv/10.1099/jgv.0.001814
2022-11-23
2024-04-26
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Suppression of innate immunity by the vaccinia virus protein N1 promotes skin microbiota expansion and increased immune infiltration following vaccination
J. Gen. Virol. 103, 001814 (2022); https://doi.org/10.1099/jgv.0.001814
/content/journal/jgv/10.1099/jgv.0.001814
/content/journal/jgv/10.1099/jgv.0.001814
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