Type I interferon imposes a TSG101/ISG15 checkpoint at the Golgi for glycoprotein trafficking during influenza virus infection.
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.
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Sumana
S
Sanyal
Joseph
J
Ashour
Takeshi
T
Maruyama
Arwen F
AF
Altenburg
Juan Jose
JJ
Cragnolini
Angelina
A
Bilate
Ana M
AM
Avalos
Lenka
L
Kundrat
Adolfo
A
García-Sastre
Hidde L
HL
Ploegh
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000276:immunology* / Q000502:physiology; D007370:Interferon Type I / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*; D057074:Virus Release; D000099177:Tsg101 Protein
D016207:Cytokines; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D006023:Glycoproteins; D007370:Interferon Type I; D014157:Transcription Factors; D014452:Ubiquitins; D000099177:Tsg101 Protein; C074034:ISG15 protein, human