title: Cell-to-cell infection by HIV contributes over half of virus infection.
abstract: Cell-to-cell viral infection, in which viruses spread through contact of infected cell with surrounding uninfected cells, has been considered as a critical mode of virus infection. However, since it is technically difficult to experimentally discriminate the two modes of viral infection, namely cell-free infection and cell-to-cell infection, the quantitative information that underlies cell-to-cell infection has yet to be elucidated, and its impact on virus spread remains unclear. To address this fundamental question in virology, we quantitatively analyzed the dynamics of cell-to-cell and cell-free human immunodeficiency virus type 1 (HIV-1) infections through experimental-mathematical investigation. Our analyses demonstrated that the cell-to-cell infection mode accounts for approximately 60% of viral infection, and this infection mode shortens the generation time of viruses by 0.9 times and increases the viral fitness by 3.9 times. Our results suggest that even a complete block of the cell-free infection would provide only a limited impact on HIV-1 spread.
authors.affiliation: Mathematical Biology Laboratory, Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.|PRESTO, Japan Science and Technology Agency, Saitama, Japan.|CREST, Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Iwami
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Junko S
authors.initials: JS
authors.lastname: Takeuchi
authors.affiliation: Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakaoka
authors.affiliation: INSERM-Genetics and Ecology of viruses, Hospital Saint Louis, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Fabrizio
authors.identifier: http://orcid.org/0000-0002-9193-7696
authors.initials: F
authors.lastname: Mammano
authors.affiliation: INSERM-Genetics and Ecology of viruses, Hospital Saint Louis, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Clavel
authors.affiliation: Graduate School of Mathematical Sciences, University of Tokyo, Tokyo, 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, Kanagawa, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Misawa
authors.affiliation: Institute of Industrial Science, University of Tokyo, Tokyo, Japan.|Graduate School of Information Science and Technology, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Aihara
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: CREST, Japan Science and Technology Agency, Saitama, Japan.|Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
mesh_terms: D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008962:Models, Theoretical; D053586:Virus Internalization; D057074:Virus Release
keywords: HIV-1; basic reproduction number; cell-free infection; cell-to-cell infection; computational biology; infectious disease; mathematical model; microbiology; systems biology; viruses