title: Electron microscopic visualization of autophagosomes induced by infection of human papillomavirus pseudovirions.
abstract: 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.
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-murayama, Tokyo 208-0011, Japan. yishii@nih.go.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
mesh_terms: D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D003470:Culture Media / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D057809:HEK293 Cells; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology; D010588:Phagosomes / Q000648:ultrastructure / Q000821:virology*; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity; D053586:Virus Internalization
chemical_list: D003470:Culture Media; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins