title: Pandemic HIV-1 Vpu overcomes intrinsic herd immunity mediated by tetherin.
abstract: Among the four groups of HIV-1 (M, N, O, and P), HIV-1M alone is pandemic and has rapidly expanded across the world. However, why HIV-1M has caused a devastating pandemic while the other groups remain contained is unclear. Interestingly, only HIV-1M Vpu, a viral protein, can robustly counteract human tetherin, which tethers budding virions. Therefore, we hypothesize that this property of HIV-1M Vpu facilitates human-to-human viral transmission. Adopting a multilayered experimental-mathematical approach, we demonstrate that HIV-1M Vpu confers a 2.38-fold increase in the prevalence of HIV-1 transmission. When Vpu activity is lost, protected human populations emerge (i.e., intrinsic herd immunity develops) through the anti-viral effect of tetherin. We also reveal that all Vpus of transmitted/founder HIV-1M viruses maintain anti-tetherin activity. These findings indicate that tetherin plays the role of a host restriction factor, providing 'intrinsic herd immunity', whereas Vpu has evolved in HIV-1M as a tetherin antagonist.
authors.affiliation: 1] Mathematical Biology Laboratory, Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Fukuoka 8128581, Japan [2] PRESTO, JST, Kawaguchi, Saitama 3320012, Japan [3] CREST, JST, Kawaguchi, Saitama 3320012, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Iwami
authors.affiliation: 1] Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto 6068507, Japan [2] CREST, JST, Kawaguchi, Saitama 3320012, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
authors.affiliation: 1] Department of Mathematical and Systems Engineering, Shizuoka University, Hamamatsu, Shizuoka 4328561, Japan [2] CREST, JST, Kawaguchi, Saitama 3320012, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Morita
authors.affiliation: 1] Graduate School of Mathematical Sciences, The University of Tokyo, Meguro-ku, Tokyo 1538914, Japan [2] CREST, JST, Kawaguchi, Saitama 3320012, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Inaba
authors.affiliation: Laboratory for Animal Health, Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa 2430034, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto 6068507, Japan.
authors.forename: Junko S
authors.initials: JS
authors.lastname: Takeuchi
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto 6068507, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto 6068507, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.affiliation: Department of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 1138510, Japan.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Ren
authors.affiliation: Mathematical Biology Laboratory, Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Fukuoka 8128581, Japan.
authors.forename: Yoh
authors.initials: Y
authors.lastname: Iwasa
authors.affiliation: 1] Institute of Industrial Science, The University of Tokyo, Meguro-ku, Tokyo 1538505, Japan [2] Graduate School of Information Science and Technology, The University of Tokyo, Meguro-ku, Tokyo 1138656, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Aihara
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto 6068507, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D058851:GPI-Linked Proteins / Q000378:metabolism; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000378:metabolism* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D032521:Immunity, Herd; D008962:Models, Theoretical; D058873:Pandemics; D056510:Position-Specific Scoring Matrices; D011485:Protein Binding; D019562:Viral Load; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins