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Event Type:  Seminar (This is an NIH Science event)
Title:  Interferon-induced Transmembrane Proteins Block Zika Virus Infection and Prevent a Non-apoptotic, Paraptosis-like Cell Death Pathway P
Description:  The clinical outcome of viral infection, the difference between survival and death of the host, rests delicately on events occurring at the molecular level of individual cells. The ‘cell-intrinsic’ arm of innate immunity prevents virus replication by detecting virus invasion and interfering with the viral life cycle. As such, cell-intrinsic immune factors, also known as host restriction factors, impose the earliest acting barriers to invading pathogens. Innate immunity controls Zika virus (ZIKV) infection and disease in most infected patients through mechanisms that remain to be understood. Furthermore, the cytopathic effects of ZIKV are widely discussed but poorly described. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family of broad spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by “implosive” cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase-independent, non-apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV-induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV-infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV-induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death. Future directions include determining whether additional antiviral functions of IFITM3, such as the reduction of HIV-1 virion fusogenicity, also manifest during flavivirus infections.
Series Name:  Immunology Interest Group Seminar Series
Videocast:  Event will be videocast LIVE on the Web
Videocast URL:
  Event will be available in the videocast ARCHIVE
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Wednesday, June 14, 2017   4:15pm - 5:30pm Add To Outlook Calendar     Add To iCal Calendar     Add To Entourage Calendar
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Name:   Dr. Alex Compton
Title:   Head, Antiviral Immunity and Resistance Section
Organization:   National Cancer Institute
State:   Maryland

Organization(s):  [NIH] Immunology Interest Group

Location:  On the main NIH Campus
Building:  Building 10
Room:  Lipsett Amphitheater
Street Address:  9000 Rockville Pike
City:  Bethesda
State:  Maryland
Zip Code:  20892

Name:   Vanja Lazarevic
Phone:   3014516882
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