Hantaviruses and Rickettsiosis Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-900, Brazil.
Neurochemistry Interactions Laboratory, Universidade Federal Fluminense, Niterói 24020-150, Brazil.
Cells. 2020 Nov 23;9(11):2525. doi: 10.3390/cells9112525.
Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.
沙粒病毒是一个多样化的新兴病毒属，包括几种导致人类严重病毒性出血热的病原体，死亡率很高。尽管这些病毒有许多相似之处，但新、旧世界病毒感染之间以及内部在致病性、免疫反应类型和病毒感染期间的分子机制方面存在重要差异。病毒完全依赖宿主细胞机制来翻译其基因组，从而进行复制和传播。miRNA 是多种生物学过程的关键因素，如抗病毒防御、致癌和细胞发育。病毒感染会对细胞 miRNA 表达谱产生深远影响，并且已经报道许多 RNA 病毒直接与细胞 miRNA 相互作用，或利用这些 miRNA 来增强其复制潜力。我们目前的研究表明，沙粒病毒感染诱导宿主细胞的代谢重编程，可能操纵细胞 microRNA。许多代谢途径，包括缬氨酸、亮氨酸和异亮氨酸生物合成、D-谷氨酰胺和 D-谷氨酸代谢、硫胺素代谢以及多种氨基酸池，都受到预测的 miRNA 的影响，这些 miRNA 将不再调节这些途径。更深入地了解沙粒状病毒处理这些信号通路的机制对于理解病毒/宿主相互作用以及通过抑制特定病理代谢途径的潜在诊断和治疗靶点至关重要。
