Antithetic effect of interferon-α on cell-free and cell-to-cell HIV-1 infection

Ryuichi Kumata, Shoya Iwanami, Katrina B. Mar, Yusuke Kakizoe, Naoko Misawa, Shinji Nakaoka, Yoshio Koyanagi, Alan S. Perelson, John W. Schoggins, Shingo Iwami, Kei Sato

Research output: Contribution to journalArticlepeer-review

Abstract

In HIV-1-infected individuals, transmitted/founder (TF) virus contributes to establish new infection and expands during the acute phase of infection, while chronic control (CC) virus emerges during the chronic phase of infection. TF viruses are more resistant to interferon-alpha (IFN-α)-mediated antiviral effects than CC virus, however, its virological relevance in infected individuals remains unclear. Here we perform an experimental-mathematical investigation and reveal that IFN-α strongly inhibits cell-to-cell infection by CC virus but only weakly affects that by TF virus. Surprisingly, IFN-α enhances cell-free infection of HIV-1, particularly that of CC virus, in a virus-cell density-dependent manner. We further demonstrate that LY6E, an IFN-stimulated gene, can contribute to the density-dependent enhancement of cell-free HIV-1 infection. Altogether, our findings suggest that the major difference between TF and CC viruses can be explained by their resistance to IFN-α-mediated inhibition of cell-to-cell infection and their sensitivity to IFN-α-mediated enhancement of cell-free infection.

Original languageEnglish (US)
Article numbere1010053
JournalPLoS Computational Biology
Volume18
Issue number4
DOIs
StatePublished - Apr 2022
Externally publishedYes

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Ecology
  • Modeling and Simulation
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

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