Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to Enable Efficient Viral Replication

Yuhei Maruzuru, Takeshi Ichinohe, Ryota Sato, Kensuke Miyake, Tokuju Okano, Toshihiko Suzuki, Takumi Koshiba, Naoto Koyanagi, Shumpei Tsuda, Mizuki Watanabe, Jun Arii, Akihisa Kato, Yasushi Kawaguchi

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24 Citations (Scopus)

Abstract

The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-18, which are critical mediators in host innate immune responses against various pathogens. Some viruses employ strategies to counteract inflammasome-mediated induction of pro-inflammatory cytokines, but their in vivo relevance is less well understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein VP22 inhibits AIM2-dependent inflammasome activation. VP22 interacts with AIM2 and prevents its oligomerization, an initial step in AIM2 inflammasome activation. A mutant virus lacking VP22 (HSV-1ΔVP22) activates AIM2 and induces IL-1β and IL-18 secretion, but these responses are lost in the absence of AIM2. Additionally, HSV-1ΔVP22 infection results in diminished viral yields in vivo, but HSV-1ΔVP22 replication is largely restored in AIM2-deficient mice. Collectively, these findings reveal a mechanism of HSV-1 evasion of the host immune response that enables efficient viral replication in vivo. Upon activation, the AIM2 inflammasome induces the release of pro-inflammatory cytokines IL-1β and IL-18, which are critical mediators in anti-microbial defense. Maruzuru et al. show that the HSV-1 tegument protein VP22 inhibits the AIM2 inflammasome by preventing its oligomerization and that this evasion strategy enables efficient viral replication in vivo.

Original languageEnglish
Pages (from-to)254-265.e7
JournalCell Host and Microbe
Volume23
Issue number2
DOIs
Publication statusPublished - Feb 14 2018

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All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

Cite this

Maruzuru, Y., Ichinohe, T., Sato, R., Miyake, K., Okano, T., Suzuki, T., ... Kawaguchi, Y. (2018). Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to Enable Efficient Viral Replication. Cell Host and Microbe, 23(2), 254-265.e7. https://doi.org/10.1016/j.chom.2017.12.014