Dierkes Rüdiger, Warnking Kathrin, Liedmann Swantje, Seyer Roman, Ludwig Stephan, Ehrhardt Christina
Institute of Molecular Virology (IMV), Centre of Molecular Virology (ZMBE), Westfälische Wilhelms-University, Münster, Germany.
PLoS One. 2014 Feb 11;9(2):e88520. doi: 10.1371/journal.pone.0088520. eCollection 2014.
The frequent emergence of new influenza viruses in the human population underlines the urgent need for antiviral therapeutics in addition to the preventative vaccination against the seasonal flu. To circumvent the development of resistance, recent antiviral approaches target cellular proteins needed by the virus for efficient replication. We investigated the contribution of the small GTPase Rac1 to the replication of influenza viruses. Inhibition of Rac1 by NSC23766 resulted in impaired replication of a wide variety of influenza viruses, including a human virus strain of the pandemic from 2009 as well as highly pathogenic avian virus strains. Furthermore, we identified a crucial role of Rac1 for the activity of the viral polymerase complex. The antiviral potential of NSC23766 was confirmed in mouse experiments, identifying Rac1 as a new cellular target for therapeutic treatment of influenza virus infections.
新型流感病毒在人群中频繁出现，这凸显了除季节性流感预防性疫苗接种外，对抗病毒疗法的迫切需求。为避免产生耐药性，近期的抗病毒方法靶向病毒高效复制所需的细胞蛋白。我们研究了小GTP酶Rac1对流感病毒复制的作用。NSC23766对Rac1的抑制导致多种流感病毒的复制受损，包括2009年大流行的一种人类病毒株以及高致病性禽流感病毒株。此外，我们确定了Rac1对病毒聚合酶复合体活性的关键作用。NSC23766的抗病毒潜力在小鼠实验中得到证实，确定Rac1为流感病毒感染治疗的新细胞靶点。
