ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction

Kei Miyakawa, Satoko Matsunaga, Kazuhiko Kanou, Atsushi Matsuzawa, Ryo Morishita, Ayumi Kudoh, Keisuke Shindo, Masaru Yokoyama, Hironori Sato, Hirokazu Kimura, Tomohiko Tamura, Naoki Yamamoto, Hidenori Ichijo, Akifumi Takaori-Kondo, Akihide Ryo

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20 Citations (Scopus)

Abstract

APOBEC3G (A3G) is an innate antiviral restriction factor that strongly inhibits the replication of human immunodeficiency virus type 1 (HIV-1). An HIV-1 accessory protein, Vif, hijacks the host ubiquitin-proteasome system to execute A3G degradation. Identification of the host pathways that obstruct the action of Vif could provide a new strategy for blocking viral replication. We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral restriction. ASK1 binds the BC-box of Vif, thereby disrupting the assembly of the Vif-ubiquitin ligase complex. Consequently, ASK1 stabilizes A3G and promotes its incorporation into viral particles, ultimately reducing viral infectivity. Furthermore, treatment with the antiretroviral drug AZT (zidovudine) induces ASK1 expression and restores the antiviral activity of A3G in HIV-1-infected cells. This study thus demonstrates a distinct function of ASK1 in restoring the host antiviral system that can be enhanced by AZT treatment.

Original languageEnglish
Article number6945
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Apr 22
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Miyakawa, K., Matsunaga, S., Kanou, K., Matsuzawa, A., Morishita, R., Kudoh, A., Shindo, K., Yokoyama, M., Sato, H., Kimura, H., Tamura, T., Yamamoto, N., Ichijo, H., Takaori-Kondo, A., & Ryo, A. (2015). ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction. Nature communications, 6, [6945]. https://doi.org/10.1038/ncomms7945