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Elife. 2015 Oct 6;4. doi: 10.7554/eLife.08150.

Cell-to-cell infection by HIV contributes over half of virus infection.

Author information

1
Mathematical Biology Laboratory, Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.
2
PRESTO, Japan Science and Technology Agency, Saitama, Japan.
3
CREST, Japan Science and Technology Agency, Saitama, Japan.
4
Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Japan.
5
Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
6
INSERM-Genetics and Ecology of viruses, Hospital Saint Louis, Paris, France.
7
Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
8
Graduate School of Mathematical Sciences, University of Tokyo, Tokyo, Japan.
9
Laboratory for Animal Health, Department of Animal Science, Faculty of Agriculture, Tokyo University of Agriculture, Kanagawa, Japan.
10
Institute of Industrial Science, University of Tokyo, Tokyo, Japan.
11
Graduate School of Information Science and Technology, University of Tokyo, Tokyo, Japan.

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.

KEYWORDS:

HIV-1; basic reproduction number; cell-free infection; cell-to-cell infection; computational biology; infectious disease; mathematical model; microbiology; systems biology; viruses

PMID:
26441404
PMCID:
PMC4592948
DOI:
10.7554/eLife.08150
[Indexed for MEDLINE]
Free PMC Article

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