Herpes Simplex Virus 1 VP22 Inhibits AIM2-Dependent Inflammasome Activation to Enable Efficient Viral Replication
| Autor: | Toshihiko Suzuki, Akihisa Kato, Ryota Sato, Yasushi Kawaguchi, Naoto Koyanagi, Tokuju Okano, Mizuki Watanabe, Shumpei Tsuda, Yuhei Maruzuru, Jun Arii, Kensuke Miyake, Takeshi Ichinohe, Takumi Koshiba |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Inflammasomes viruses Interleukin-1beta Herpesvirus 1 Human Biology Virus Replication medicine.disease_cause Microbiology Virus Cell Line Mice 03 medical and health sciences AIM2 Immune system Virology Chlorocebus aethiops NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Humans RNA Small Interfering Vero Cells Mice Knockout Viral Structural Proteins Innate immune system 030102 biochemistry & molecular biology Interleukin-18 Inflammasome Viral tegument Immunity Innate Cell biology DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology Herpes simplex virus Viral replication DNA Viral Female RNA Interference Parasitology medicine.drug |
| Zdroj: | Cell Host & Microbe. 23:254-265.e7 |
| ISSN: | 1931-3128 |
| Popis: | 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 . |
| Databáze: | OpenAIRE |
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