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Main Authors: Zeng, Qiongzhen, Li, Menghe, Gao, Hengyuan, Zheng, Kai, Zou, Weixiangmin, La, Caiwenjie, Fu, Leyi, Liu, Xiaodi, Wang, Yifei, Liu, Kaisheng
Format: Artículo científico
Language:en
Published: The Journal of infectious diseases 2026
Subjects:
Online Access:https://pubmed.ncbi.nlm.nih.gov/40795270/
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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/