Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA 90033, USA.
School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA.
Viruses. 2020 Dec 18;12(12):1466. doi: 10.3390/v12121466.
Positive-strand RNA viruses universally remodel host intracellular membranes to form membrane-bound viral replication complexes, where viral offspring RNAs are synthesized. In the majority of cases, viral replication proteins are targeted to and play critical roles in the modulation of the designated organelle membranes. Many viral replication proteins do not have transmembrane domains, but contain single or multiple amphipathic alpha-helices. It has been conventionally recognized that these helices serve as an anchor for viral replication protein to be associated with membranes. We report here that a peptide representing the amphipathic α-helix at the N-terminus of the poliovirus 2C protein not only binds to liposomes, but also remodels spherical liposomes into tubules. The membrane remodeling ability of this amphipathic alpha-helix is similar to that recognized in other amphipathic alpha-helices from cellular proteins involved in membrane remodeling, such as BAR domain proteins. Mutations affecting the hydrophobic face of the amphipathic alpha-helix severely compromised membrane remodeling of vesicles with physiologically relevant phospholipid composition. These mutations also affected the ability of poliovirus to form plaques indicative of reduced viral replication, further underscoring the importance of membrane remodeling by the amphipathic alpha-helix in possible relation to the formation of viral replication complexes.
正链 RNA 病毒普遍重塑宿主细胞内的膜结构，形成膜结合的病毒复制复合物，在此复合物中合成病毒子代 RNA。在大多数情况下，病毒复制蛋白被靶向并在特定细胞器膜的调节中发挥关键作用。许多病毒复制蛋白没有跨膜结构域，但含有单个或多个两亲性α-螺旋。传统上认为，这些螺旋作为病毒复制蛋白与膜结合的锚定点。我们在此报告，代表脊髓灰质炎病毒 2C 蛋白 N 端的疏水性 α-螺旋的肽不仅与脂质体结合，而且还将球形脂质体重塑成管状。这种疏水性 α-螺旋的膜重塑能力与其他参与膜重塑的细胞蛋白中的疏水性 α-螺旋相似，如 BAR 结构域蛋白。影响疏水性 α-螺旋疏水面的突变严重损害了具有生理相关磷脂组成的囊泡的膜重塑。这些突变还影响了脊髓灰质炎病毒形成斑块的能力，这表明病毒复制减少，进一步强调了疏水性 α-螺旋的膜重塑在可能与病毒复制复合物形成的关系中的重要性。
