Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-murayama, Tokyo 208-0011, Japan.
Biochem Biophys Res Commun. 2013 Apr 19;433(4):385-9. doi: 10.1016/j.bbrc.2013.02.130. Epub 2013 Mar 26.
Autophagy is a bulk degradation process for subcellular proteins and organelles to manage cell starvation. Autophagy is associated with the formation of autophagosomes and further functions as a defense mechanism against infection by various pathogens. Human papillomavirus (HPV) infection induces an autophagy response, such as up-regulation of marker proteins for autophagy, in host keratinocytes. However, direct microscopic evidence for autophagy induction by HPV infection is still lacking. Here, I report an electron microscopic analysis of autophagosomes elicited by the entry of HPV pseudovirions (PsVs). HeLa cells showed enhanced infectivity for PsVs of HPV type 16 (16PsVs) when treated with an autophagy inhibitor, suggesting the involvement of autophagy in HPV infection. In HeLa cells inoculated with 16PsVs, transmission electron microscopy showed the presence of cup-shaped, double-membrane vesicles (phagophores) and double-membrane-bound vesicles, which are typical structures of autophagosomes. These double-membrane vesicles displayed a large lumen volume and incorporated 10-50 16PsVs particles in the lumen. These results demonstrate that autophagy is indeed induced during the HPV16 entry process and imply that autophagosomes are generated from the plasma membrane by HPV infection.
自噬是一种用于降解细胞内蛋白质和细胞器的批量降解过程，可帮助细胞在饥饿时存活。自噬与自噬体的形成有关，并进一步作为一种防御机制，抵御各种病原体的感染。人乳头瘤病毒（HPV）感染会诱导宿主角质细胞发生自噬反应，如自噬标记蛋白的上调。然而，HPV 感染诱导自噬的确切证据仍然缺乏。在这里，我报告了 HPV 假病毒（PsV）进入时自噬体的电子显微镜分析。当用自噬抑制剂处理时，HeLa 细胞对 HPV 型 16（16PsV）的 PsV 的感染性增强，表明自噬参与 HPV 感染。在接种 16PsV 的 HeLa 细胞中，透射电子显微镜显示存在杯状双层膜囊泡（吞噬体）和双层膜结合囊泡，这是自噬体的典型结构。这些双层膜囊泡显示出较大的腔体积，并在腔中容纳了 10-50 个 16PsV 颗粒。这些结果表明，HPV16 进入过程中确实诱导了自噬，并暗示自噬体是由 HPV 感染从质膜产生的。
