Department of Molecular Genetics and Microbiology, UF Health Cancer Center, College of Medicine, University of Florida, Gainesville, Florida, USA.
Department of Molecular Genetics and Microbiology, UF Health Cancer Center, College of Medicine, University of Florida, Gainesville, Florida, USA
mBio. 2019 Jul 30;10(4):e00996-19. doi: 10.1128/mBio.00996-19.
Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies, including B cell lymphomas. , these viruses infect B cells and manipulate B cell biology to establish lifelong latent infection. To accomplish this, gammaherpesviruses employ an array of gene products, including microRNAs (miRNAs). Although numerous host mRNA targets of gammaherpesvirus miRNAs have been identified, the relevance of repression of these targets remains elusive due to species restriction. Murine gammaherpesvirus 68 (MHV68) provides a robust virus-host system to dissect the function of conserved gammaherpesvirus genetic elements. We identified here MHV68 - as critical for infection and then validated host (Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using novel, target-specific shRNA-expressing viruses, we determined that repression was essential for germinal center B cell infection. These findings provide the first demonstration of the biological significance of repression of a specific host mRNA by a gammaherpesvirus miRNA. Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies. , these viruses infect B cells and manipulate B cell biology to establish lifelong infection. To accomplish this, gammaherpesviruses employ an array of gene products, including miRNAs, short noncoding RNAs that bind to and repress protein synthesis from specific target mRNAs. The relevance of repression of targets of gammaherpesvirus miRNAs remains highly elusive. Here, we identified a murine gammaherpesvirus miRNA as critical for infection and validated the host mRNA (Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using a novel technology, we demonstrated that repression of was essential for infection of the critical B cell reservoir. These findings provide the first demonstration of the significance of repression of a specific host mRNA by a gammaherpesvirus miRNA.
γ疱疹病毒，包括人类病原体 EBV（Epstein-Barr 病毒）和 KSHV（卡波济肉瘤相关疱疹病毒），直接促成了多种类型的恶性肿瘤的发生，包括 B 细胞淋巴瘤。这些病毒感染 B 细胞并操纵 B 细胞生物学以建立终身潜伏感染。为了实现这一目标，γ疱疹病毒采用了一系列基因产物，包括 microRNAs（miRNAs）。尽管已经鉴定出许多γ疱疹病毒 miRNA 的宿主 mRNA 靶标，但由于物种限制，这些靶标的抑制相关性仍然难以捉摸。鼠γ疱疹病毒 68（MHV68）提供了一个强大的病毒-宿主系统，用于剖析保守的γ疱疹病毒遗传元件的功能。我们在这里鉴定出 MHV68 对于感染是至关重要的，然后验证了宿主 mRNA（Ewing 肉瘤断点区域 1）是该 miRNA 的主要靶标。使用新型、靶特异性 shRNA 表达病毒，我们确定了抑制对于生发中心 B 细胞感染是必不可少的。这些发现首次证明了 γ疱疹病毒 miRNA 对特定宿主 mRNA 的抑制具有生物学意义。γ疱疹病毒，包括人类病原体 EBV（Epstein-Barr 病毒）和 KSHV（卡波济肉瘤相关疱疹病毒），直接促成了多种类型的恶性肿瘤的发生。这些病毒感染 B 细胞并操纵 B 细胞生物学以建立终身感染。为了实现这一目标，γ疱疹病毒采用了一系列基因产物，包括 miRNAs，即短的非编码 RNA，它们与特定的靶 mRNA 结合并抑制其蛋白合成。γ疱疹病毒 miRNA 靶标的抑制相关性仍然高度难以捉摸。在这里，我们鉴定出一种鼠γ疱疹病毒 miRNA 对于感染是至关重要的，并验证了宿主 mRNA（Ewing 肉瘤断点区域 1）是该 miRNA 的主要靶标。我们使用一种新的技术，证明了对的抑制对于关键 B 细胞储库的感染是必不可少的。这些发现首次证明了 γ疱疹病毒 miRNA 对特定宿主 mRNA 的抑制具有重要意义。
Zotero 插件
