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

Shingo Iwami,Naoko Misawa,Hisashi Inaba,Yoshio Koyanagi,Junko S Takeuchi,Tomoko Kobayashi,Kazuyuki Aihara,Fabrizio Mammano,Shinji Nakaoka,Kei Sato,François Clavel

doi:10.7554/elife.08150

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.

Highlights

In in vitro cell cultures and in infected individuals, viruses may display two types of replication strategies: cell-free infection and cell-to-cell infection (Sattentau, 2008; Martin and Sattentau, 2009; Talbert-Slagle et al, 2014)
Through experimental-mathematical investigation, here we quantitatively elucidated the dynamics of the cell-to-cell and cell-free human immunodeficiency virus type 1 (HIV-1) infection modes (Figure 2 and Table 1)
Based on our calculated values of these three indexes, we found that about 60% of the viral infection is attributed to the cell-to-cell infection in the in vitro cell culture system (Table 1), which is consistent with previous estimation by Komarova and Wodarz (2013), Komarova et al (2013a), and Komarova et al (2013b)

Summary

Introduction

In in vitro cell cultures and in infected individuals, viruses may display two types of replication strategies: cell-free infection and cell-to-cell infection (Sattentau, 2008; Martin and Sattentau, 2009; Talbert-Slagle et al, 2014). Both transmission means require the assembly of infectious virus particles (Monel et al, 2012), which are released in the extracellular medium for cell-free transmission, or concentrated in the confined space of cell-to-cell contacts between an infected cell and bystander target cells in the case of cell-to-cell transmission.

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Results

Conclusion