부산대학교 도서관

Positive-stranded (+)RNA viruses greatly exploit host cells to support viral replication. However, unlike many other pathogens, (+)RNA viruses code for only a limited number of genes, making them highly dependent on numerous co-opted host factors for supporting viral replication and other viral processes during their infections. This excessive dependence on subverted host factors, however, renders (+)RNA viruses vulnerable to host restriction factors that could block virus replication. Interestingly, cellular ATP-dependent DEAD-box RNA helicases could promote or inhibit the replication of Tomato bushy stunt virus (TBSV) replication. However, it is currently unknown what features make a particular DEAD-box helicase either pro-viral or antiviral. In this work, we succeeded in reversing the viral function of the antiviral DDX17-like RH30 DEAD-box helicase by converting it to a pro-viral helicase. We also turned the pro-viral DDX3-like RH20 helicase into an antiviral helicase through deletion of a unique N-terminal domain. We demonstrate that in the absence of the N-terminal domain, the core helicase domain becomes unhinged, showing altered specificity in unwinding viral RNA duplexes containing cis-acting replication elements. The discovery of the sequence plasticity of DEAD-box helicases that can alter recognition of different cis-acting RNA elements in the viral genome illustrates the evolutionary potential of RNA helicases in the arms race between viruses and their hosts, including key roles of RNA helicases in plant innate immunity. Overall, these findings open up the possibility to turn the pro-viral host factors into antiviral factors, thus increasing the potential antiviral arsenal of the host for the benefit of agriculture and health science. Author summary: The largest group of eukaryotic viruses, the positive-strand RNA viruses, depends greatly on co-opting host components to support their replication. This dependence on host factors by these viruses also makes them vulnerable to antiviral factors. This is well-illustrated in case of tombusviruses, a small RNA viruses of plants. Tombusviruses co-opt many host factors to support various steps in their replication. Among these host factors are cellular DEAD-box helicases, which help remodeling viral RNA structures during the RNA replication process. However, similar cellular helicases remodel the viral RNAs incorrectly, making them antiviral or restriction factors. To gain insights into what makes a particular DEAD-box helicase pro-viral or antiviral, in this work, we converted the antiviral plant RH30 helicase into a pro-viral helicase through modifying the N-terminal sequences. We also succeeded to turn the originally pro-viral plant RH20 helicase into an antiviral helicase using a similar strategy. By characterizing the newly acquired functions of these helicases, we obtained valuable insights into what features make these helicases either pro-viral or antiviral. These discoveries have implications to better understand the arms race between viruses and hosts. In addition, it opens up the opportunity to generate new antiviral tools by converting pro-viral host factors into antiviral factors, thus enhancing our molecular tools against the ever-evolving RNA viruses. [ABSTRACT FROM AUTHOR]