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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
The Journal of infectious diseases
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40795270/ |
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| _version_ | 1868266167289774081 |
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| author | Zeng, Qiongzhen Li, Menghe Gao, Hengyuan Zheng, Kai Zou, Weixiangmin La, Caiwenjie Fu, Leyi Liu, Xiaodi Wang, Yifei Liu, Kaisheng |
| author_facet | Zeng, Qiongzhen Li, Menghe Gao, Hengyuan Zheng, Kai Zou, Weixiangmin La, Caiwenjie Fu, Leyi Liu, Xiaodi Wang, Yifei Liu, Kaisheng Zeng, Qiongzhen Li, Menghe Gao, Hengyuan Zheng, Kai Zou, Weixiangmin La, Caiwenjie Fu, Leyi Liu, Xiaodi Wang, Yifei Liu, Kaisheng |
| collection | PubMed - marine biology |
| contents | Histone Deacetylase 6 Regulates α-Tubulin to Inhibit the Stimulator of Interferon Genes/NLR Family Pyrin Domain-Containing 3-Mediated Microglial Pyroptosis Induced by Herpes Simplex Virus Type 1 Infection. Zeng, Qiongzhen Li, Menghe Gao, Hengyuan Zheng, Kai Zou, Weixiangmin La, Caiwenjie Fu, Leyi Liu, Xiaodi Wang, Yifei Liu, Kaisheng Pyroptosis Animals Herpesvirus 1, Human Histone Deacetylase 6 NLR Family, Pyrin Domain-Containing 3 Protein Tubulin Herpes Simplex Microglia Mice Phosphate-Binding Proteins Inflammasomes Mice, Inbred C57BL Intracellular Signaling Peptides and Proteins Humans Gasdermins Microglia constitute the first line of defense that initiates immune responses against herpes simplex virus type 1 (HSV-1) infection. In HSV-1 infection, the regulatory function of the NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis in microglia, which acts as an intrinsic antiviral immune response, remains unclear. This study investigated the interaction between pyroptosis and HSV-1 infection. Gasdermin D (GSDMD) is cleaved in HSV-1 infection in vitro and in vivo. Gasdermin D knockdown inhibited pyroptosis and lactate dehydrogenase (LDH) release but enhanced HSV-1 infection. Histone deacetylase 6 (HDAC6) knockdown and inhibition of HDAC6 deacetylase activity by tubacin promoted NLRP3 inflammasome activation, LDH, and mature IL-1β release and microglial pyroptosis, weakening HSV-1 infection. Blocking α-tubulin acetylation attenuated the stimulator of interferon genes-NLRP3 interaction, counteracting the increased GSDMD cleavage by HDAC6 inhibitors and resulting in increased susceptibility to HSV-1 infection. Our findings reveal that HDAC6 inactivates NLRP3-mediated microglial pyroptosis to facilitate HSV-1 infection, providing a new potential strategy for effective antiviral immunotherapy. |
| format | Artículo científico |
| id | pubmed_40795270 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | The Journal of infectious diseases |
| record_format | pubmed |
| spellingShingle | Histone Deacetylase 6 Regulates α-Tubulin to Inhibit the Stimulator of Interferon Genes/NLR Family Pyrin Domain-Containing 3-Mediated Microglial Pyroptosis Induced by Herpes Simplex Virus Type 1 Infection. Zeng, Qiongzhen Li, Menghe Gao, Hengyuan Zheng, Kai Zou, Weixiangmin La, Caiwenjie Fu, Leyi Liu, Xiaodi Wang, Yifei Liu, Kaisheng Pyroptosis Animals Herpesvirus 1, Human Histone Deacetylase 6 NLR Family, Pyrin Domain-Containing 3 Protein Tubulin Herpes Simplex Microglia Mice Phosphate-Binding Proteins Inflammasomes Mice, Inbred C57BL Intracellular Signaling Peptides and Proteins Humans Gasdermins Histone Deacetylase 6 Regulates α-Tubulin to Inhibit the Stimulator of Interferon Genes/NLR Family Pyrin Domain-Containing 3-Mediated Microglial Pyroptosis Induced by Herpes Simplex Virus Type 1 Infection. Zeng, Qiongzhen Li, Menghe Gao, Hengyuan Zheng, Kai Zou, Weixiangmin La, Caiwenjie Fu, Leyi Liu, Xiaodi Wang, Yifei Liu, Kaisheng Pyroptosis Animals Herpesvirus 1, Human Histone Deacetylase 6 NLR Family, Pyrin Domain-Containing 3 Protein Tubulin Herpes Simplex Microglia Mice Phosphate-Binding Proteins Inflammasomes Mice, Inbred C57BL Intracellular Signaling Peptides and Proteins Humans Gasdermins Microglia constitute the first line of defense that initiates immune responses against herpes simplex virus type 1 (HSV-1) infection. In HSV-1 infection, the regulatory function of the NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis in microglia, which acts as an intrinsic antiviral immune response, remains unclear. This study investigated the interaction between pyroptosis and HSV-1 infection. Gasdermin D (GSDMD) is cleaved in HSV-1 infection in vitro and in vivo. Gasdermin D knockdown inhibited pyroptosis and lactate dehydrogenase (LDH) release but enhanced HSV-1 infection. Histone deacetylase 6 (HDAC6) knockdown and inhibition of HDAC6 deacetylase activity by tubacin promoted NLRP3 inflammasome activation, LDH, and mature IL-1β release and microglial pyroptosis, weakening HSV-1 infection. Blocking α-tubulin acetylation attenuated the stimulator of interferon genes-NLRP3 interaction, counteracting the increased GSDMD cleavage by HDAC6 inhibitors and resulting in increased susceptibility to HSV-1 infection. Our findings reveal that HDAC6 inactivates NLRP3-mediated microglial pyroptosis to facilitate HSV-1 infection, providing a new potential strategy for effective antiviral immunotherapy. |
| title | Histone Deacetylase 6 Regulates α-Tubulin to Inhibit the Stimulator of Interferon Genes/NLR Family Pyrin Domain-Containing 3-Mediated Microglial Pyroptosis Induced by Herpes Simplex Virus Type 1 Infection. |
| topic | Pyroptosis Animals Herpesvirus 1, Human Histone Deacetylase 6 NLR Family, Pyrin Domain-Containing 3 Protein Tubulin Herpes Simplex Microglia Mice Phosphate-Binding Proteins Inflammasomes Mice, Inbred C57BL Intracellular Signaling Peptides and Proteins Humans Gasdermins |
| url | https://pubmed.ncbi.nlm.nih.gov/40795270/ |