Role of EXT1 and Glycosaminoglycans in the Early Stage of Filovirus Entry

Journal of Virology
Aileen O'HearnLijun Rong

Abstract

Filoviruses, including both Ebola virus (EBOV) and Marburg virus (MARV), can infect humans and other animals, causing hemorrhagic fever with a high mortality rate. Entry of these viruses into the host is mediated by a single filoviral glycoprotein (GP). GP is composed of two subunits: GP1, which is responsible for attachment and binding to receptor(s) on susceptible cells, and GP2, which mediates viral and cell membrane fusion. Although numerous host factors have been implicated in the entry process, the initial attachment receptor(s) has not been well defined. In this report, we demonstrate that exostosin 1 (EXT1), which is involved in biosynthesis of heparan sulfate (HS), plays a role in filovirus entry. Expression knockdown of EXT1 by small interfering RNAs (siRNAs) impairs GP-mediated pseudoviral entry and that of infectious EBOV and MARV in tissue cultured cells. Furthermore, HS, heparin, and other related glycosaminoglycans (GAGs), to different extents, can bind to and block GP-mediated viral entry and that of infectious filoviruses. These results strongly suggest that HS and other related GAGs are attachment receptors that are utilized by filoviruses for entry and infection. These GAGs may have therapeutic potential in t...Continue Reading

References

Nov 29, 1975·British Medical Journal·J S GearJ H Gear
Mar 1, 1992·The Journal of Cell Biology·M T ShiehP G Spear
Feb 1, 1995·The Journal of General Virology·S BeckerH D Klenk
Jan 11, 2001·Journal of Virology·T GiroglouM Sapp
Jun 7, 2002·Journal of Virology·Carmen P AlvarezRafael Delgado
Apr 2, 2004·Cellular Microbiology·Patricia G Spear
Mar 30, 2005·Journal of Virology·Balaji ManicassamyLijun Rong
Apr 16, 2005·Science·Kartik ChandranJames M Cunningham
Apr 6, 2006·The Journal of Biological Chemistry·Jens H KuhnMichael Farzan
Sep 23, 2006·Virology·Balaji ManicassamyLijun Rong
Sep 29, 2006·Journal of Virology·Masayuki ShimojimaYoshihiro Kawaoka
Dec 19, 2008·Chemical Biology & Drug Design·Neha S Gandhi, Ricardo L Mancera
Apr 4, 2009·Virology Journal·Ying GuoLijun Rong
Jun 10, 2009·Virology Journal·Balaji Manicassamy, Lijun Rong
Jan 7, 2010·Virology Journal·Tan Letian, Zhang Tianyu
May 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Andrew S KondratowiczWendy Maury
Aug 26, 2011·Nature·Jan E CaretteThijn R Brummelkamp
Oct 19, 2011·The Journal of Infectious Diseases·Paul RoddyMatthias Borchert
Oct 19, 2011·The Journal of Infectious Diseases·Mark G KortepeterMike Bray
Mar 8, 2012·The EMBO Journal·Emily Happy MillerKartik Chandran
Sep 28, 2012·Journal of Virology·S M de BoerB J Bosch
Jan 11, 2013·Journal of Virology·Beatriz SalvadorGraham Simmons
Sep 21, 2013·Frontiers in Microbiology·Eri Nakayama, Masayuki Saijo
Aug 30, 2014·Nature·Xiangguo QiuGary P Kobinger

❮ Previous
Next ❯

Citations

May 26, 2015·Trends in Microbiology·Lucas T Jae, Thijn R Brummelkamp
May 6, 2016·Annual Review of Genomics and Human Genetics·Angela L Rasmussen
Sep 2, 2016·Virology Journal·Lisa HenßBarbara S Schnierle
Apr 12, 2017·Scientific Reports·Daniel R Beniac, Timothy F Booth
Dec 9, 2015·Antimicrobial Agents and Chemotherapy·Joanna S SaidTomas Bergström
Aug 8, 2018·Laboratory Medicine·Caterina M Miraglia
May 28, 2019·F1000Research·Judith OlejnikAdam J Hume
Dec 18, 2018·Frontiers in Pharmacology·Dominik D KaltenbachVaibhav Tiwari
Dec 7, 2019·Journal of Autoimmunity·Manuel RojasJuan-Manuel Anaya
Sep 5, 2020·Journal of Medicinal Chemistry·Laura CooperRui Xiong
Apr 15, 2021·Seminars in Thrombosis and Hemostasis·Raghuram KogantiDeepak Shukla

❮ Previous
Next ❯

Related Concepts

Related Feeds

Argentine Hemorrhagic Fever

Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by junín virus (JUNV), a member of the arenaviridae family. Discover the latest research on AHF here.