TY - JOUR
T1 - Type i interferon imposes a TSG101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection
AU - Sanyal, Sumana
AU - Ashour, Joseph
AU - Maruyama, Takeshi
AU - Altenburg, Arwen F.
AU - Cragnolini, Juan Jose
AU - Bilate, Angelina
AU - Avalos, Ana M.
AU - Kundrat, Lenka
AU - García-Sastre, Adolfo
AU - Ploegh, Hidde L.
N1 - Funding Information:
This work was funded by the National Institutes of Health (RO1 grants AI033456 and AI087879 to H.L.P.) and Sanofi Pasteur (H.L.P.) and partially by the Center for Research on Influenza Pathogenesis (NIAID CEIRS contract HHSN266200700010C and NIAID grant U19 AI083025 to A.G.-S.). For technical assistance and discussions, the authors acknowledge Richard Cadagan, Fikadu Tafesse, Carla Guimaraes, and Lee Kim Swee.
PY - 2013/11/13
Y1 - 2013/11/13
N2 - Several enveloped viruses exploit host pathways, such as the cellular endosomal sorting complex required for transport (ESCRT) machinery, for their assembly and release. The influenza A virus (IAV) matrix protein binds to the ESCRT-I complex, although the involvement of early ESCRT proteins such as Tsg101 in IAV trafficking remain to be established. We find that Tsg101 can facilitate IAV trafficking, but this is effectively restricted by the interferon (IFN)-stimulated protein ISG15. Cytosol from type I IFN-treated cells abolished IAV hemagglutinin (HA) transport to the cell surface in infected semi-intact cells. This inhibition required Tsg101 and could be relieved with deISGylases. Tsg101 is itself ISGylated in IFN-treated cells. Upon infection, intact Tsg101-deficient cells obtained by CRISPR-Cas9 genome editing were defective in the surface display of HA and for infectious virion release. These data support the IFN-induced generation of a Tsg101- and ISG15-dependent checkpoint in the secretory pathway that compromises influenza virus release.
AB - Several enveloped viruses exploit host pathways, such as the cellular endosomal sorting complex required for transport (ESCRT) machinery, for their assembly and release. The influenza A virus (IAV) matrix protein binds to the ESCRT-I complex, although the involvement of early ESCRT proteins such as Tsg101 in IAV trafficking remain to be established. We find that Tsg101 can facilitate IAV trafficking, but this is effectively restricted by the interferon (IFN)-stimulated protein ISG15. Cytosol from type I IFN-treated cells abolished IAV hemagglutinin (HA) transport to the cell surface in infected semi-intact cells. This inhibition required Tsg101 and could be relieved with deISGylases. Tsg101 is itself ISGylated in IFN-treated cells. Upon infection, intact Tsg101-deficient cells obtained by CRISPR-Cas9 genome editing were defective in the surface display of HA and for infectious virion release. These data support the IFN-induced generation of a Tsg101- and ISG15-dependent checkpoint in the secretory pathway that compromises influenza virus release.
UR - http://www.scopus.com/inward/record.url?scp=84887957632&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2013.10.011
DO - 10.1016/j.chom.2013.10.011
M3 - Article
C2 - 24237697
AN - SCOPUS:84887957632
SN - 1931-3128
VL - 14
SP - 510
EP - 521
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 5
ER -