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

• Published in: eLife 2015-10, Vol.4
• Main Authors: Iwami, Shingo, Takeuchi, Junko S, Nakaoka, Shinji, Mammano, Fabrizio, Clavel, François, Inaba, Hisashi, Kobayashi, Tomoko, Misawa, Naoko, Aihara, Kazuyuki, Koyanagi, Yoshio, Sato, Kei
• Format: Article
• Language: English
• Subjects: basic reproduction number; cell-free infection; cell-to-cell infection; Computational and Systems Biology; HIV Infections - virology; HIV-1; HIV-1 - physiology; Humans; Jurkat Cells; mathematical model; Microbiology and Infectious Disease; Models, Theoretical; Virus Internalization; Virus Release
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.08150

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.