title: Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus.
abstract: Despite major advances in our understanding of many aspects of human papillomavirus (HPV) biology, HPV entry is poorly understood. To identify cellular genes required for HPV entry, we conducted a genome-wide screen for siRNAs that inhibited infection of HeLa cells by HPV16 pseudovirus. Many retrograde transport factors were required for efficient infection, including multiple subunits of the retromer, which initiates retrograde transport from the endosome to the trans-Golgi network (TGN). The retromer has not been previously implicated in virus entry. Furthermore, HPV16 capsid proteins arrive in the TGN/Golgi in a retromer-dependent fashion during entry, and incoming HPV proteins form a stable complex with retromer subunits. We propose that HPV16 directly engages the retromer at the early or late endosome and traffics to the TGN/Golgi via the retrograde pathway during cell entry. These results provide important insights into HPV entry, identify numerous potential antiviral targets, and suggest that the role of the retromer in infection by other viruses should be assessed.
authors.affiliation: Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520-8011, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Lipovsky
authors.forename: Andreea
authors.initials: A
authors.lastname: Popa
authors.forename: Genaro
authors.initials: G
authors.lastname: Pimienta
authors.forename: Michael
authors.initials: M
authors.lastname: Wyler
authors.forename: Ashima
authors.initials: A
authors.lastname: Bhan
authors.forename: Leena
authors.initials: L
authors.lastname: Kuruvilla
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Guie
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Poffenberger
authors.forename: Christian D S
authors.initials: CD
authors.lastname: Nelson
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Atwood
authors.forename: Daniel
authors.initials: D
authors.lastname: DiMaio
mesh_terms: D015894:Genome, Human / Q000235:genetics*; D006056:Golgi Apparatus / Q000821:virology; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000502:physiology; D006801:Humans; D027383:Papillomaviridae / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000821:virology; D011485:Protein Binding; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D015203:Reproducibility of Results; D033921:Vesicular Transport Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D034741:RNA, Small Interfering; D033921:Vesicular Transport Proteins; D014764:Viral Proteins