[PDF][PDF] Herpes simplex virus 1 VP22 inhibits AIM2-dependent inflammasome activation to enable efficient viral replication

Y Maruzuru, T Ichinohe, R Sato, K Miyake, T Okano… - Cell host & …, 2018 - cell.com
Y Maruzuru, T Ichinohe, R Sato, K Miyake, T Okano, T Suzuki, T Koshiba, N Koyanagi…
Cell host & microbe, 2018cell.com
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 …
Summary
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.
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