Transcriptional Regulation of Latency-Associated Transcripts (LATs) of Herpes Simplex Viruses
Transcriptional Regulation of Latency-Associated Transcripts (LATs) of Herpes Simplex Viruses
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单纯疱疹病毒潜伏相关转录本 (LAT) 的转录调控
DOI：
10.7150/jca.40186
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发表时间：
2020
影响因子：
3.9
通讯作者：
Hong-Wu Xin
中科院分区：
文献类型：
--
作者：
Ying Zhang;Qiang Xin;Jun-Yi Zhang;Ying-Ying Wang;Jun-Ting Cheng;Wen-Qi Cai;Zi-Wen Han;Yang Zhou;Shu-Zhong Cui;Xiao-Chun Peng;Xian-Wang Wang;Zhaowu Ma;Ying Xiang;Xiu-Lan Su;Hong-Wu Xin
单纯疱疹病毒(HSV)会引起唇疱疹和生殖器疱疹，并可在神经元中建立终身潜伏感染。一种工程的溶瘤单纯疱疹病毒(OHSV)最近被批准用于临床治疗肿瘤。HSV潜伏期相关转录本(LAT)与潜伏感染有关，但LAT转录调控的报道很少。为了更好地治疗HSV感染和肿瘤，我们对我们最近分离的新株HSV-1-LXMW的DNA编码基因LAT和转录调控区LAT进行了测序，并与其他4株HSV-1和2株HSV-2进行了序列比较分析。LATs的系统发育分析表明，HSV-1-LXMW与英国格拉斯哥MRC大学的HSV-1-17在进化上很接近。首次利用基于权重矩阵的程序匹配和多序列比对的方法，我们鉴定了与9个转录因子结合的HSV LAT转录调控序列：AP-1、C-Rel、Comp1、E2F、Hary、HfH-3、Kr、TCF11/MAFG、v-Myb。有趣的是，这些转录调控序列和因子在HSV-1和HSV-2的LAT中要么是保守的，要么是唯一的，这表明它们具有潜在的功能。此外，文献分析发现，转录因子v-myb和AP-1家族成员Jund在调节HSV基因转录方面具有功能，包括LAT转录。我们首次发现了七个新的HSV LATs转录因子及其相应的转录调控序列。根据我们的发现和其他报告，我们提出了HSV潜伏感染的启动和维持的潜在机制。我们的发现可能对我们理解HSV潜伏期和设计更好的溶瘤性HSV具有重要意义。
Herpes simplex viruses (HSVs) cause cold sores and genital herpes and can establish lifelong latent infection in neurons. An engineered oncolytic HSV (oHSV) has recently been approved to treat tumors in clinics. HSV latency-associated transcripts (LATs) are associated with the latent infection, but LAT transcriptional regulation was seldom reported. For a better treatment of HSV infection and tumors, here we sequenced the LAT encoding DNA and LAT transcription regulatory region of our recently isolated new strain HSV-1-LXMW and did comparative analysis of the sequences together with those of other four HSV-1 and two HSV-2 strains. Phylogenetic analysis of LATs revealed that HSV-1-LXMW is evolutionarily close to HSV-1-17 from MRC University, Glasgow, UK. For the first time, Using a weight matrix-based program Match and multi-sequences alignment of the 6 HSV strains, we identified HSV LAT transcription regulatory sequences that bind to 9 transcription factors: AP-1, C-REL, Comp1, E2F, Hairy, HFH-3, Kr, TCF11/MAFG, v-Myb. Interestingly, these transcription regulatory sequences and factors are either conserved or unique among LATs of HSV-1 and HSV-2, suggesting they are potentially functional. Furthermore, literature analysis found that the transcription factors v-myb and AP-1 family member JunD are functional in regulating HSV gene transcription, including LAT transcription. For the first time, we discovered seven novel transcription factors and their corresponding transcription regulatory sequences of HSV LATs. Based on our findings and other reports, we proposed potential mechanisms of the initiation and maintenance of HSV latent infection. Our findings may have significant implication in our understanding of HSV latency and engineering of better oncolytic HSVs.