Downregulation of β1 Integrins by Ebola Virus Glycoprotein: Implication for Virus Entry

Takada, Ayato; Watanabe, Shinji; Ito, Hiroshi; Okazaki, Katsunori; Kida, Hiroshi; Kawaoka, Yoshihiro

doi:10.1006/viro.2000.0601

Cited by 175 publications

(166 citation statements)

References 14 publications

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“…filoviruses to host cells has been associated with several attachment factors [80][81][82][83][84][85] , but entry and deposition of replication machinery for both Ebolaviruses and Marburgviruses have been directly linked to intravesicular cleavage of GP by host proteases, such as cathepsins 86 , and subsequent fusion of viral GP with the host protein Niemann-Pick C1 (NPC1) 87,88 .…”

Section: R E V I E W Smentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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Section: R E V I E W Smentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

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“…4d, Supplementary Table 1). Among these TMDs are known interactors of GP, such as b1-integrin 24 . Nine proteins involved in the immune response (for example, the a-chain of HLA class II) were also identified.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the interaction between b1-integrin and GP was shown to contribute to the loss of adhesion of GP-expressing cells 7,24 . Furthermore, a role for the GP 2 subunit in counteracting interferon-induced antiviral response via the protein tetherin (BST-2) has been proposed 25 .…”

mentioning

confidence: 99%

Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol

et al. 2015

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The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, Ebola fusogenic glycoprotein (GP) has been associated with the detachment of infected cells and eventually leads to vascular leakage and haemorrhagic fever. Here we report that the membrane-anchored GP is sufficient to induce the detachment of adherent cells. The results show that the detachment induced through either full-length GP 1,2 or the subunit GP 2 depends on cholesterol and the structure of the transmembrane domain. These data reveal a novel molecular mechanism in which GP regulates Ebola virus assembly and suggest that cholesterol-reducing agents could be useful as therapeutics to counteract GP-mediated cell detachment.

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“…However, the C-type lectin asialoglycoprotein receptor (27,28), DC-SIGN (29,30), hMGL (31), L-SIGN (29,30), and LSECtin (32), as well as other molecules, including folate receptor-␣ (33) and ␤1 integrins (15), have been shown or suggested to enhance filovirus cell entry. Subtle differences between marburgvirus and ebolavirus infection efficiencies in different cell lines or following glycosidase or protease treatment have led to the suggestion that these viruses utilize distinct receptors or entry mechanisms (5).…”

mentioning

confidence: 99%

Conserved Receptor-binding Domains of Lake Victoria Marburgvirus and Zaire Ebolavirus Bind a Common Receptor

Kuhn

Radoshitzky

Guth

et al. 2006

Journal of Biological Chemistry

120

136

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The GP 1,2 envelope glycoproteins (GP) of filoviruses (marburg-and ebolaviruses) mediate cell-surface attachment, membrane fusion, and entry into permissive cells. Here we show that a 151-amino acid fragment of the Lake Victoria marburgvirus GP 1 subunit bound filoviruspermissive cell lines more efficiently than full-length GP 1 . An homologous 148-amino acid fragment of the Zaire ebolavirus GP 1 subunit similarly bound the same cell lines more efficiently than a series of longer GP 1 truncation variants. Neither the marburgvirus GP 1 fragment nor that of ebolavirus bound a nonpermissive lymphocyte cell line. Both fragments specifically inhibited replication of infectious Zaire ebolavirus, as well as entry of retroviruses pseudotyped with either Lake Victoria marburgvirus or Zaire ebolavirus GP 1,2 . These studies identify the receptor-binding domains of both viruses, indicate that these viruses utilize a common receptor, and suggest that a single small molecule or vaccine can be developed to inhibit infection of all filoviruses.

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Downregulation of β1 Integrins by Ebola Virus Glycoprotein: Implication for Virus Entry

Cited by 175 publications

References 14 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol

Conserved Receptor-binding Domains of Lake Victoria Marburgvirus and Zaire Ebolavirus Bind a Common Receptor

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