Folate Receptor-α Is a Cofactor for Cellular Entry by Marburg and Ebola Viruses

Chan, Stephen Y.; Empig, Cyril; Welte, Frank J.; Speck, Roberto F.; Schmaljohn, Alan L.; Kreisberg, Jason F.; Goldsmith, Mark A.

doi:10.1016/s0092-8674(01)00418-4

Cited by 197 publications

(126 citation statements)

References 36 publications

Supporting

Mentioning

119

Contrasting

Order By: Relevance

“…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: Vaccination Of Humansmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

View full text Add to dashboard Cite

| 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...

show abstract

Section: Vaccination Of Humansmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

View full text Add to dashboard Cite

show abstract

“…VP24 is essential for the formation of nucleocapsids composed of NP, VP35, and viral RNA (20). The only viral surface glycoprotein, GP, plays a role in viral attachment and entry (21)(22)(23)(24).…”

mentioning

confidence: 99%

Generation of biologically contained Ebola viruses

Halfmann

Kim

Ebihara

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

120

163

View full text Add to dashboard Cite

Ebola virus (EBOV), a public health concern in Africa and a potential biological weapon, is classified as a biosafety level-4 agent because of its high mortality rate and the lack of approved vaccines and antivirals. Basic research into the mechanisms of EBOV pathogenicity and the development of effective countermeasures are restricted by the current biosafety classification of EBOVs. We therefore developed biologically contained EBOV that express a reporter gene instead of the VP30 gene, which encodes an essential transcription factor. A Vero cell line that stably expresses VP30 provides this essential protein in trans and biologically confines the virus to its complete replication cycle in this cell line. This complementation approach is highly efficient because biologically contained EBOVs lacking the VP30 gene grow to titers similar to those obtained with wild-type virus. Moreover, EBOVs lacking the VP30 gene are indistinguishable in their morphology from wild-type virus and are genetically stable, as determined by sequence analysis after seven serial passages in VP30-expressing Vero cells. We propose that this system provides a safe means to handle EBOV outside a biosafety level-4 facility and will stimulate critical studies on the EBOV life cycle as well as large-scale screening efforts for compounds with activity against this lethal virus.antiviral screening ͉ reverse genetics ͉ vaccine development

show abstract

“…Target cells include myeloid cells such as monocyte/macrophages, dendritic cells (Bosio et al, manuscript submitted), hepatocytes, and endothelial cells [2]. In contrast, lymphocytes are resistant to filovirus infections [2,7]. Although information on the nature of cellular receptors for filoviruses is limited, such receptor(s) appear to be protein(s), most likely glycosylated, with a lineage-restricted expression pattern [8,9].…”

Section: Viral Receptorsmentioning

confidence: 99%

“…Due to the highly pathogenic nature of filoviruses and their classification as biosafety level-4 agents, detailed entry studies for these viruses have been only performed by pseudotyping. Using such an approach, folate receptor a (FRa) was recently identified as a cofactor for filovirus entry [7]. FRa renders Jurkat cells permissive to filovirus GP-pseudotyped HIV, although these FRa-expressing cells are poorly infected by live virus [7].…”

Section: Viral Receptorsmentioning

confidence: 99%

Molecular Mechanisms of Filovirus Cellular Trafficking

Aman¹,

Bosio²,

Panchal³

et al. 2003

Self Cite

View full text Add to dashboard Cite

The filoviruses, Ebola and Marburg, are two of the most pathogenic viruses, causing lethal hemorrhagic fever in humans. Recent discoveries suggest that filoviruses, along with other phylogenetically or functionally related viruses, utilize a complex mechanism of replication exploiting multiple cellular components including lipid rafts, endocytic compartments, and vacuolar protein sorting machinery. In this review, we summarize these recent findings and discuss the implications for vaccine and therapeutics development.

show abstract

Folate Receptor-α Is a Cofactor for Cellular Entry by Marburg and Ebola Viruses

Cited by 197 publications

References 36 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Generation of biologically contained Ebola viruses

Molecular Mechanisms of Filovirus Cellular Trafficking

Contact Info

Product

Resources

About