Cell-to-cell infection by HIV contributes over half of virus infection
Shingo Iwami,
Junko S Takeuchi,
Shinji Nakaoka,
Fabrizio Mammano,
François Clavel,
Hisashi Inaba,
Tomoko Kobayashi,
Naoko Misawa,
Kazuyuki Aihara,
Yoshio Koyanagi,
Kei Sato
Affiliations
Shingo Iwami
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
Junko S Takeuchi
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan
Shinji Nakaoka
Graduate School of Medicine, University of Tokyo, Tokyo, Japan
INSERM-Genetics and Ecology of viruses, Hospital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France
François Clavel
INSERM-Genetics and Ecology of viruses, Hospital Saint Louis, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France
Hisashi Inaba
Graduate School of Mathematical Sciences, University of Tokyo, Tokyo, Japan
Tomoko Kobayashi
Laboratory for Animal Health, Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, Kanagawa, Japan
Naoko Misawa
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan
Kazuyuki Aihara
Institute of Industrial Science, University of Tokyo, Tokyo, Japan; Graduate School of Information Science and Technology, University of Tokyo, Tokyo, Japan
Yoshio Koyanagi
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan
Kei Sato
CREST, Japan Science and Technology Agency, Saitama, Japan; Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan
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.
