Leong Jessica, Husain Matloob
Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
Viruses. 2024 Dec 29;17(1):33. doi: 10.3390/v17010033.
Influenza A virus (IAV) remains a pandemic threat. Particularly, the evolution and increased interspecies and intercontinental transmission of avian IAV H5N1 subtype highlight the importance of continuously studying the IAV and identifying the determinants of its pathogenesis. Host innate antiviral response is the first line of defense against IAV infection, and the transcription factor, the signal transducer and activator of transcription 3 (STAT3), has emerged as a critical component of this response. Also, histone deacetylase 1 (HDAC1) and HDAC2 have been identified as important components of IAV-induced host innate antiviral response. Upon IAV infection, STAT3 is activated and translocated to the nucleus to initiate the transcription of innate response genes. Also, the HDAC1 and HDAC2 are localized to the nucleus. In this study, we sought to investigate the role of HDAC1 and HDAC2 in IAV-induced STAT3 nuclear translocation. We employed a quantitative confocal microscopy approach and analyzed the nuclear translocation of plasmid-expressed STAT3-GFP in IAV-infected cells depleted with the expression of HDAC1 or HDAC2. We found that the depletion of both HDAC1 and HDAC2 expression inhibits the IAV-induced nuclear translocation of STAT3-GFP. These findings will help elucidate the significance of the emerging role of acetylation in IAV infection and disease severity.
甲型流感病毒(IAV)仍然是一种大流行威胁。特别是,禽流感病毒H5N1亚型的进化以及种间和洲际传播的增加凸显了持续研究IAV并确定其发病机制决定因素的重要性。宿主先天性抗病毒反应是抵御IAV感染的第一道防线,转录因子信号转导和转录激活因子3(STAT3)已成为这一反应的关键组成部分。此外,组蛋白去乙酰化酶1(HDAC1)和HDAC2已被确定为IAV诱导的宿主先天性抗病毒反应的重要组成部分。IAV感染后,STAT3被激活并转运至细胞核,启动先天性反应基因的转录。此外,HDAC1和HDAC2定位于细胞核。在本研究中,我们试图研究HDAC1和HDAC2在IAV诱导的STAT3核转位中的作用。我们采用定量共聚焦显微镜方法,分析了在HDAC1或HDAC2表达被耗尽的IAV感染细胞中质粒表达的STAT3-GFP的核转位情况。我们发现,HDAC1和HDAC2表达的耗尽均抑制了IAV诱导的STAT3-GFP核转位。这些发现将有助于阐明乙酰化在IAV感染和疾病严重程度中新兴作用的重要性。