Glycosylation and oligomerization of the spike protein of marburg virus

Feldmann, Heinz; Will, Christiane; Schikore, M.; Slenczka, Werner; Klenk, Hans‐Dieter

doi:10.1016/0042-6822(91)90680-a

Cited by 113 publications

(92 citation statements)

References 16 publications

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“…VP40 directly interacts with cellular endosomal trafficking elements and is key for viral budding 94 . GP requires post-translational modifications in the endoplasmic reticulum and Golgi processes and hence follows a different trafficking pathway to the plasma membrane than do the other viral proteins [95][96][97] . Unique to members of the Ebolavirus genus, an artefact of transcriptional editing of the GP gene allows for the production of several nonstructural GP derivatives, each of which is thought to contribute to pathogenesis in a different way, some of which may have direct relevance to interventions specific to Ebolavirus infections [97][98][99][100][101] .…”

Section: Replicationmentioning

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: Replicationmentioning

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 following lectins bound to agarose beads (Sigma) were used: Helix pomatia and Vicia villosa B4 lectins, which bind unsubstituted N-acetyl galactosamine (GalNAc); Arachis hypogaea lectin, which binds galactose (1-3)-N-acetyl galactosamine (GalGalNAc) when not substituted by sialic acid, and Lens culinaris lectin, which binds alpha mannosyl residues (Hammarstrom & Kabat, 1971 ;Lotan et at., 1975;Tollefsen & Kornfeld, 1983;Lundstrum et al, 1987a, b;Feldmann et al, 1991). Cell lysates in RIPA buffer were mixed for 1 h at 4 °C with a one-tenth volume of lectin-agarose beads, washed four times in RIPA buffer, and heated at 95 °C for 5 rain to dissociate the bound glycoprotein.…”

Section: Methodsmentioning

confidence: 99%

“…The G ectodomain is rich in proline (13 ~, compared to an average of 5 ~) and serine and threonine residues (30~ combined, compared to an average of 13 ~) and does not contain cysteine residues apart from those flanking the conserved domain. The G protein also contains a substantial amount of O-linked sugars which, among non-segmented negative-strand viruses, have also been reported only in the filoviruses (Feldmann et al, 1991). The ectodomain contains more than 70 serine residues as potential acceptor sites; their number and distribution suggests that the G protein might contain numerous side-chains scattered on either side of the conserved domain, and this model has some support from studies of truncated G proteins (Olmsted et al, 1989;Garcia-Barreno et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Oligomerization and post-translational processing of glycoprotein G of human respiratory syncytial virus: altered O-glycosylation in the presence of brefeldin A

Collins

Mottet²

1992

Journal of General Virology

103

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“…Several cellular coreceptors have been proposed to be involved in binding and entry of EBOV and MARV, including several C-type lectins such as dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin (DC-SIGN) [35,[43][44][45][46][47]. However, the exact nature of and requirement for these cellular receptors is unknown, and it is possible that the heavily glycosylated GP alone can bind and mediate entry via multiple cell-surface lectins [48][49][50][51]. …”

Section: Biology Of Filovirus Infectionsmentioning

confidence: 99%

Filovirus-like particles as vaccines and discovery tools

Warfield

Swenson

Demmin

et al. 2005

Expert Review of Vaccines

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Ebola and Marburg viruses are members of the family Filoviridae, which cause severe hemorrhagic fevers in humans. Filovirus outbreaks have been sporadic, with mortality rates currently ranging from 30 to 90%. Unfortunately, there is no efficacious human therapy or vaccine available to treat disease caused by either Ebola or Marburg virus infection. Expression of the filovirus matrix protein, VP40, is sufficient to drive spontaneous production and release of virus-like particles (VLPs) that resemble the distinctively filamentous infectious virions. The addition of other filovirus proteins, including virion proteins (VP)24, 30 and 35 and glycoprotein, increases the efficiency of VLP production and results in particles containing multiple filovirus antigens. Vaccination with Ebola or Marburg VLPs containing glycoprotein and VP40 completely protects rodents from lethal challenge with the homologous virus. These candidate vaccines are currently being tested for immunogenicity and efficacy in nonhuman primates. Furthermore, the Ebola and Marburg VLPs are being used as a surrogate model to further understand the filovirus life cycle, with the goal of developing rationally designed vaccines and therapeutics. Thus, in addition to their use as a vaccine, VLPs are currently being used as tools to learn lessons about filovirus pathogenesis, immunology, replication and assembly requirements.Expert Rev. Vaccines 4(3), 429-440 (2005) Ebola (EBOV) and Marburg (MARV) viruses are the only members of the family Filoviridae, and were named according to their filamentous shape. EBOV and MARV cause acute and rapidly progressive hemorrhagic fever with mortality rates in humans of up to 90% [1,2]. The reservoir for filoviruses is unknown, although the consumption of monkey meat is often associated with onset of disease. Animals ranging from insects to mammals have been analyzed in the hopes of identifying a carrier, but to no avail [3]. After exposure, the onset of clinical symptoms can be as short as 2 days and as long as 21, although most infected humans and nonhuman primates die within 7-10 days of exposure [4]. In addition to hemorrhage and bleeding, other symptoms of filovirus infection include fever, headache, generalized myalgia, prostration, conjunctivitis, rash, lymphadenopathy, pharyngitis and edema [5].Filoviruses are considered serious public health threats, and are classified as biosafety level (BSL)-4 agents and Category A biothreat agents by the US Centers for Disease Control and Prevention [6,101]. Features that characterize filoviruses as a significant global health risk include high morbidity and mortality rates, potential for person-to-person transmission, relative stability in the environment, and feasibility of large-scale production. Additionally, the filoviruses have a low infectious dose, an extremely rapid rate of replication and can be easily transmitted, including via aerosols [4,7,8]. Bolstering the fear of their use as bioterrorism agents, several hemorrhagic fever viruses have a history of state-sponsor...

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Glycosylation and oligomerization of the spike protein of marburg virus

Cited by 113 publications

References 16 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Oligomerization and post-translational processing of glycoprotein G of human respiratory syncytial virus: altered O-glycosylation in the presence of brefeldin A

Filovirus-like particles as vaccines and discovery tools

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