title: Inhibition of nuclear entry of HPV16 pseudovirus-packaged DNA by an anti-HPV16 L2 neutralizing antibody.
abstract: Rabbit anti-HPV16 L2 serum (anti-P56/75) neutralizes multiple oncogenic human papillomaviruses (HPVs). We inoculated HeLa cells with HPV16 pseudovirus (16PV) and with anti-P56/75-bound 16PV (16PV-Ab). Both 16PV and 16PV-Ab attached equally well to the cell surface. However, the cell-attached L1 protein of 16PV became trypsin-resistant after incubation at 37°C, whereas approximately 20% of the cell-attached 16PV-Ab L1 remained trypsin-sensitive. Confocal microscopy of HeLa cells inoculated with 16PV revealed packaged DNA in the nucleus at 22h after inoculation; however, nuclear DNA was not detected in cells inoculated with 16PV-Ab. Electron microscopy of HeLa cells inoculated with 16PV showed particles located in multivesicular bodies, lamellar bodies, and the cytosol after 4h; no cytosolic particles were detected after inoculation with 16PV-Ab. These data suggest that anti-P56/75 inhibits HPV infection partly by blocking viral entry and primarily by blocking the transport of the viral genome to the nucleus.
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan. yishii@nih.go.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kondo
authors.forename: Takamasa
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Mori
authors.forename: Tadahito
authors.initials: T
authors.lastname: Kanda
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000494:pharmacology*; D036022:Capsid Proteins / Q000276:immunology*; D002460:Cell Line; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D011817:Rabbits; D019065:Virus Assembly / Q000187:drug effects
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D004279:DNA, Viral; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral