title: IFITM3-containing exosome as a novel mediator for anti-viral response in dengue virus infection.
abstract: Interferon-inducible transmembrane proteins 1, 2 and 3 (IFITM1, IFITM2 and IFITM3) have recently been identified as potent antiviral effectors that function to suppress the entry of a broad range of enveloped viruses and modulate cellular tropism independent of viral receptor expression. However, the antiviral effect and mechanisms of IFITMs in response to viral infections remain incompletely understood and characterized. In this work, we focused our investigation on the function of the extracellular IFITM3 protein. In cell models of DENV-2 infection, we found that IFITM3 contributed to both the baseline and interferon-induced inhibition of DENV entry. Most importantly, our study for the first time demonstrated the presence of IFITM-containing exosome in the extracellular environment, and identified an ability of cellular exosome to intercellularly deliver IFITM3 and thus transmit its antiviral effect from infected to non-infected cells. Thus, our findings provide new insights in the basic mechanisms underlying the actions of IFITM3, which might lead to future development of exosome-mediated anti-viral strategies using IFITM3 as a therapeutic agent. Conceivably, variations in the basal and inducible levels of IFITMs, as well as in intracellular and extracellular levels of IFITMs, might predict the severity of dengue virus infections among individuals or across species.
authors.affiliation: Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, China; Guangdong Province Key Laboratory of Functional Molecules in Oceanic Microorganism (Sun Yat-sen University), Bureau of Education, Guangzhou, China; Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhenjian
authors.initials: Z
authors.lastname: He
authors.forename: Jie
authors.initials: J
authors.lastname: Yuan
authors.forename: Weitao
authors.initials: W
authors.lastname: Wen
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Hu
authors.forename: Cuiji
authors.initials: C
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Haijing
authors.initials: H
authors.lastname: Deng
authors.forename: Shaowei
authors.initials: S
authors.lastname: Liao
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology* / Q000502:physiology; D055354:Exosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D000998:Antiviral Agents; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins