The Interferon-Induced Exonuclease ISG20 Exerts Antiviral Activity through Upregulation of Type I Interferon Response Proteins

MSphere
Christopher M WeissWilliam B Klimstra

Abstract

Type I interferon (IFN)-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20-kDa ISG ISG20 is a nuclear 3'-5' exonuclease with preference for single-stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Although the exonuclease activity of ISG20 has been shown to degrade viral RNA in vitro, evidence has yet to be presented that virus inhibition in cells requires this activity. Here, we utilized a combination of an inducible, ectopic expression system and newly generated Isg20-/- mice to investigate mechanisms and consequences of ISG20-mediated restriction. Ectopically expressed ISG20 localized primarily to Cajal bodies in the nucleus and restricted replication of chikungunya and Venezuelan equine encephalitis viruses. Although restriction by ISG20 was associated with inhibition of translation of infecting genomic RNA, degradation of viral RNAs was not observed. Instead, translation inhibition of viral RNA was associated with ISG20-induced upregulation of over 100 other genes, many of which encode known antiviral ...Continue Reading

References

Aug 1, 1997·The Journal of Biological Chemistry·C GongoraN Mechti
Jun 1, 1965·Proceedings of the Society for Experimental Biology and Medicine·H J WEISSS B RUSS
Dec 18, 2003·Proceedings of the National Academy of Sciences of the United States of America·Sarah M McWhirterTom Maniatis
Apr 1, 2006·Chromosoma·David Stanek, Karla M Neugebauer
Dec 26, 2006·Vector Borne and Zoonotic Diseases·Konstantin TsetsarkinDana L Vanlandingham
Jan 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Deborah J LenschowHerbert Whiting Virgin
Feb 19, 2008·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Youhua Hao, Dongliang Yang
Aug 30, 2008·Biochimica Et Biophysica Acta·Glenn E Morris
Oct 8, 2008·Immunological Reviews·Kate D Ryman, William B Klimstra
Jan 23, 2010·Nature Reviews. Molecular Cell Biology·Richard J JacksonTatyana V Pestova
Feb 4, 2010·The Journal of Experimental Medicine·Clémentine SchilteMatthew L Albert
Jun 4, 2010·Journal of Virology·Joy GardnerAndreas Suhrbier
Feb 14, 2012·Current Opinion in Virology·John W Schoggins, Charles M Rice
Dec 12, 2012·Nature Biotechnology·Cole TrapnellLior Pachter
Dec 20, 2013·Nature·Derek W TrobaughWilliam B Klimstra
Feb 1, 2014·Science·Jennifer L HydeMichael S Diamond
Feb 22, 2014·Annual Review of Immunology·William M SchneiderCharles M Rice
Aug 1, 2014·Journal of Virology·Thomas E Morrison

❮ Previous
Next ❯

Citations

Jul 10, 2019·Annual Review of Virology·John W Schoggins
Jun 4, 2020·Vaccines·Marie-France Martin, Sébastien Nisole
Dec 29, 2020·Frontiers in Immunology·Emily Yang, Melody M H Li
Feb 24, 2021·RNA Biology·Lukasz MarkiewiczPawel J Sikorski
Apr 4, 2021·Viruses·Joe McKellarCaroline Goujon
Apr 9, 2021·Virologica Sinica·Xiaoyong ChenGuangzhi Tong
Jul 13, 2021·Reviews in Medical Virology·Mina Mobini KeshehSomayeh Shokri
Dec 11, 2021·The Journal of General Virology·Basheer A AlDaifStephen B Fleming

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE115729

Methods Mentioned

BETA
confocal microscopy
fluorescence microscopy
PCR
transfections
RNA-seq
transfection
immunoprecipitation assay
in vitro transcription
protein assay
Knockout

Software Mentioned

GraphPad PRISM
Cufflinks
Cuffdiff
Tophat

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.