title: APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity.
abstract: Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) proteins are cellular DNA/RNA-editing enzymes that play pivotal roles in the innate immune response to viral infection. APOBEC3 (A3) proteins were reported to hypermutate the genome of human papillomavirus 16 (HPV16), the causative agent of cervical cancer. However, hypermutation did not affect viral DNA maintenance, leaving the exact role of A3 against HPV infection elusive. Here we examine whether A3 proteins affect the virion assembly using an HPV16 pseudovirion (PsV) production system, in which PsVs are assembled from its capsid proteins L1/L2 encapsidating a reporter plasmid in 293FT cells. We found that co-expression of A3A or A3C in 293FT cells greatly reduced the infectivity of PsV. The reduced infectivity of PsV assembled in the presence of A3A, but not A3C, was attributed to the decreased copy number of the encapsidated reporter plasmid. On the other hand, A3C, but not A3A, efficiently bound to L1 in co-immunoprecipitation assays, which suggests that this physical interaction may lead to reduced infectivity of PsV assembled in the presence of A3C. These results provide mechanistic insights into A3s' inhibitory effects on the assembly phase of the HPV16 virion.
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Md Monjurul
authors.initials: MM
authors.lastname: Ahasan
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kousho
authors.initials: K
authors.lastname: Wakae
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan; Division of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, 116001, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kitamura
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Guangyan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Koura
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Imayasu
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kousei
authors.initials: K
authors.lastname: Hanaoka
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan; Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Izumo, Shimane 693-8501, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
authors.affiliation: Division of Otorhinolaryngology and Head and Neck Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Division of Otorhinolaryngology and Head and Neck Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-murayama, Tokyo 208-0011, Japan.
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Mori
authors.affiliation: Pathogen Genomics Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-murayama, Tokyo 208-0011, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Kukimoto
authors.affiliation: Department of Molecular Genetics, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8640, Japan. Electronic address: muramatu@med.kanazawa-u.ac.jp.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
mesh_terms: D036022:Capsid Proteins / Q000502:physiology; D003564:Cytidine Deaminase / Q000235:genetics / Q000502:physiology*; D005260:Female; D016679:Genome, Viral; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000502:physiology; D011485:Protein Binding; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014771:Virion / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D014774:Virulence; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D011506:Proteins; C063317:L1 protein, Human papillomavirus type 16; C121399:APOBEC3A protein, human; C495795:APOBEC3C protein, human; D003564:Cytidine Deaminase
keywords: APOBEC3; Antiviral activity; HPV16; Pseudovirion