CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, 100101, China.
Protein Cell. 2014 May;5(5):348-56. doi: 10.1007/s13238-014-0039-y. Epub 2014 Apr 12.
During virus infection, viral RNAs and mRNAs function as blueprints for viral protein synthesis and possibly as pathogen-associated molecular patterns (PAMPs) in innate immunity. Here, considering recent research progress in microRNAs (miRNAs) and competitive endogenous RNAs (ceRNAs), we speculate that viral RNAs act as sponges and can sequester endogenous miRNAs within infected cells, thus cross-regulating the stability and translational efficiency of host mRNAs with shared miRNA response elements. This cross-talk and these reciprocal interactions between viral RNAs and host mRNAs are termed "competitive viral and host RNAs" (cvhRNAs). We further provide recent experimental evidence for the existence of cvhRNAs networks in hepatitis B virus (HBV), as well as Herpesvirus saimiri (HVS), lytic murine cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) infections. In addition, the cvhRNA hypothesis also predicts possible cross-regulation between host and other viruses, such as hepatitis C virus (HCV), HIV, influenza virus, human papillomaviruses (HPV). Since the interaction between miRNAs and viral RNAs also inevitably leads to repression of viral RNA function, we speculate that virus may evolve either to employ cvhRNA networks or to avoid miRNA targeting for optimal fitness within the host. CvhRNA networks may therefore play a fundamental role in the regulation of viral replication, infection establishment, and viral pathogenesis.
在病毒感染过程中，病毒 RNA 和 mRNA 不仅作为病毒蛋白合成的模板，还可能作为先天免疫中的病原体相关分子模式（PAMPs）。在这里，考虑到 microRNAs（miRNAs）和竞争性内源 RNA（ceRNAs）的最新研究进展，我们推测病毒 RNA 作为海绵，可以在感染细胞内隔离内源性 miRNAs，从而跨调控具有共享 miRNA 反应元件的宿主 mRNA 的稳定性和翻译效率。这种病毒 RNA 和宿主 mRNA 之间的串扰和相互作用被称为“竞争性病毒和宿主 RNA”（cvhRNAs）。我们进一步提供了乙型肝炎病毒（HBV）、猴疱疹病毒（HVS）、裂解型鼠巨细胞病毒（MCMV）和人巨细胞病毒（HCMV）感染中 cvhRNAs 网络存在的最新实验证据。此外，cvhRNA 假说还预测了宿主和其他病毒（如丙型肝炎病毒（HCV）、HIV、流感病毒、人乳头瘤病毒（HPV））之间可能存在交叉调控。由于 miRNA 和病毒 RNA 之间的相互作用也不可避免地导致病毒 RNA 功能受到抑制，我们推测病毒可能进化到利用 cvhRNA 网络或避免 miRNA 靶向以在宿主中获得最佳适应性。因此，cvhRNA 网络可能在病毒复制、感染建立和病毒发病机制的调控中发挥基础性作用。
