Histone deacetylase 6’s function in viral infection, innate immunity, and disease: latest advances

Qu, Min; Zhang, Huijun; Cheng, Peng; Wubshet, Ashenafi Kiros; Yin, Xin; Wang, Xiangwei; Sun, Yinyan

doi:10.3389/fimmu.2023.1216548

Cited by 3 publications

(1 citation statement)

References 171 publications

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“…Taken together, these data suggest that functional HDAC6 negatively regulates the protein expression of NS5 in the cytoplasm, which is predominantly detected in the nucleus, and prevents the aberrant acetylation of MTs and p62 accumulation observed when the ZIKV NS5 protein is overexpressed. Thus, it is plausible that, as occurs with HIV, IAV and other viruses [91,92,94,[98][99][100][101][104][105][106]190,191], HDAC6 could also be involved in the control of ZIKV NS5-driven viral RNA replication and virus production at the late stages of the viral cycle and that the ZIKV NS5 protein targets the p62/HDAC6 aggresome pathway to ensure viral persistence.…”

Section: Discussionmentioning

confidence: 99%

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor

Pérez-Yanes,

Lorenzo-Sánchez,

Cabrera-Rodríguez

et al. 2024

Cells

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Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital Zika syndrome and microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is the largest product encoded by ZIKV-RNA and is important for replication and immune evasion. Here, we studied the potential effects of NS5 on microtubules (MTs) and autophagy flux, together with the interplay of NS5 with histone deacetylase 6 (HDAC6). Fluorescence microscopy, biochemical cell-fractionation combined with the use of HDAC6 mutants, chemical inhibitors and RNA interference indicated that NS5 accumulates in nuclear structures and strongly promotes the acetylation of MTs that aberrantly reorganize in nested structures. Similarly, NS5 accumulates the p62 protein, an autophagic-flux marker. Therefore, NS5 alters events that are under the control of the autophagic tubulin-deacetylase HDAC6. HDAC6 appears to degrade NS5 by autophagy in a deacetylase- and BUZ domain-dependent manner and to control the cytoplasmic expression of NS5. Moreover, NS5 inhibits RNA-mediated RIG-I interferon (IFN) production, resulting in greater activity when autophagy is inhibited (i.e., effect correlated with NS5 stability). Therefore, it is conceivable that NS5 contributes to cell toxicity and pathogenesis, evading the IFN-immune response by overcoming HDAC6 functions. HDAC6 has emerged as an anti-ZIKV factor by targeting NS5.

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Section: Discussionmentioning

confidence: 99%

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor

Pérez-Yanes,

Lorenzo-Sánchez,

Cabrera-Rodríguez

et al. 2024

Cells

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Histone deacetylase 8 promotes innate antiviral immunity through deacetylation of RIG-I

Zhang,

Liu,

Liu

et al. 2024

Front. Cell. Infect. Microbiol.

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Histone deacetylates family proteins have been studied for their function in regulating viral replication by deacetylating non-histone proteins. RIG-I (Retinoic acid-inducible gene I) is a critical protein in RNA virus-induced innate antiviral signaling pathways. Our previous research showed that HDAC8 (histone deacetylase 8) involved in innate antiviral immune response, but the underlying mechanism during virus infection is still unclear. In this study, we showed that HDAC8 was involved in the regulation of vesicular stomatitis virus (VSV) replication. Over-expression of HDAC8 inhibited while knockdown promoted VSV replication. Further exploration demonstrated that HDAC8 interacted with and deacetylated RIG-I, which eventually lead to enhance innate antiviral immune response. Collectively, our data clearly demonstrated that HDAC8 inhibited VSV replication by promoting RIG-I mediated interferon production and downstream signaling pathway.

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Comparative transcriptome analysis of resistant and susceptible watermelon genotypes reveals the role of RNAi, callose, proteinase, and cell wall in squash vein yellowing virus resistance

Kumar,

Chanda,

Adkins

et al. 2024

Front. Plant Sci.

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Watermelon (Citrullus lanatus) is the third largest fruit crop in the world in term of production. However, it is susceptible to several viruses. Watermelon vine decline (WVD), caused by whitefly-transmitted squash vein yellowing virus (SqVYV), is a disease that has caused over $60 million in losses in the US and continues to occur regularly in southeastern states. Understanding the molecular mechanisms underlying resistance to SqVYV is important for effective disease management. A time-course transcriptomic analysis was conducted on resistant (392291-VDR) and susceptible (Crimson Sweet) watermelon genotypes inoculated with SqVYV. Significantly higher levels of SqVYV were observed over time in the susceptible compared to the resistant genotype. The plasmodesmata callose binding protein (PDCB) gene, which is responsible for increased callose deposition in the plasmodesmata, was more highly expressed in the resistant genotype than in the susceptible genotype before and after inoculation, suggesting the inhibition of cell-to-cell movement of SqVYV. The potential role of the RNA interference (RNAi) pathway was observed in the resistant genotype based on differential expression of eukaryotic initiation factor (eIF), translin, DICER, ribosome inactivating proteins, RNA-dependent RNA polymerase (RDR), and Argonaute (AGO) genes after inoculation. The significant differential expression of hormone-related genes, including those involved in the ethylene, jasmonic acid, auxin, cytokinin, gibberellin, and salicylic acid signaling pathways, was observed, emphasizing their regulatory roles in the defense response. Genes regulating pectin metabolism, cellulose synthesis, cell growth and development, xenobiotic metabolism, and lignin biosynthesis were overexpressed in the susceptible genotype, suggesting that alterations in cell wall integrity and growth processes result in disease symptom development. These findings will be helpful for further functional studies and the development of SqVYV-resistant watermelon cultivars.

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Histone deacetylase 6’s function in viral infection, innate immunity, and disease: latest advances

Cited by 3 publications

References 171 publications

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor

The ZIKV NS5 Protein Aberrantly Alters the Tubulin Cytoskeleton, Induces the Accumulation of Autophagic p62 and Affects IFN Production: HDAC6 Has Emerged as an Anti-NS5/ZIKV Factor

Histone deacetylase 8 promotes innate antiviral immunity through deacetylation of RIG-I

Comparative transcriptome analysis of resistant and susceptible watermelon genotypes reveals the role of RNAi, callose, proteinase, and cell wall in squash vein yellowing virus resistance

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