Department I of Internal Medicine, University of Cologne, 50924 Cologne, Germany.
Virology. 2011 Jan 5;409(1):77-83. doi: 10.1016/j.virol.2010.09.025. Epub 2010 Oct 25.
The unique region of the VP1 capsid protein of adeno-associated viruses (AAV) in common with autonomously replicating parvoviruses comprises a secreted phospholipase A2 (sPLA2) homology domain. While the sPLA2 domain of Minute Virus of Mice has recently been shown to mediate endosomal escape by lipolytic pore formation, experimental evidence for a similar function in AAV infection is still lacking. Here, we explored the function of the sPLA2 domain of AAV by making use of the serotype 2 mutant (76)HD/AN. The sPLA2 defect in (76)HD/AN, which severely impairs AAV's infectivity, could be complemented in trans by co-infection with wild-type AAV2. Furthermore, co-infection with endosomolytically active, but not with inactive adenoviral variants partially rescued (76)HD/AN, providing the first evidence for a function of this domain in endosomal escape of incoming AAV particles.
腺相关病毒 (AAV) 的 VP1 衣壳蛋白与自主复制的细小病毒共有一个分泌型 PLA2（sPLA2）同源结构域。最近有研究表明，鼠细小病毒的 sPLA2 结构域通过形成脂解孔介导内体逃逸，但 AAV 感染中是否存在类似功能的证据仍然缺乏。在这里，我们通过利用血清型 2 突变体 (76)HD/AN 来探索 AAV 的 sPLA2 结构域的功能。(76)HD/AN 的 sPLA2 缺陷严重损害了 AAV 的感染力，但通过与野生型 AAV2 共感染可以在转染中得到补偿。此外，内体溶酶体活性的腺病毒变体而非非活性腺病毒变体的共感染部分挽救了 (76)HD/AN，这首次提供了该结构域在进入 AAV 颗粒的内体逃逸中的作用的证据。
