TY - JOUR
T1 - ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction
AU - Miyakawa, Kei
AU - Matsunaga, Satoko
AU - Kanou, Kazuhiko
AU - Matsuzawa, Atsushi
AU - Morishita, Ryo
AU - Kudoh, Ayumi
AU - Shindo, Keisuke
AU - Yokoyama, Masaru
AU - Sato, Hironori
AU - Kimura, Hirokazu
AU - Tamura, Tomohiko
AU - Yamamoto, Naoki
AU - Ichijo, Hidenori
AU - Takaori-Kondo, Akifumi
AU - Ryo, Akihide
N1 - Funding Information:
HIV-1 Vif monoclonal antibody (#319) and pNLGRINFQ were obtained from Dr Michael H. Malim and from Drs Tomozumi Imamichi and H. Clifford Lane, respectively, through the NIH AIDS Reagent Program. We thank Dr Wataru Sugiura (National Hospital Organization Nagoya Medical Center) for reagents and Mayu Miyamoto for technical support. This work was supported in part by the Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program and grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to A.R.).
Publisher Copyright:
© 2015 Macmillan Publishers Limited. All rights reserved.
PY - 2015/4/22
Y1 - 2015/4/22
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms7945
DO - 10.1038/ncomms7945
M3 - Article
C2 - 25901786
AN - SCOPUS:84928803755
SN - 2041-1723
VL - 6
JO - Nature Communications
JF - Nature Communications
M1 - 6945
ER -
