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| Open AccessSelective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats
The ecology of Ebola virus (EBOV) is still largely unclear. Here, the authors show that Angolan freetailed bats are selectively permissive to EBOV infection, but not to other filoviruses, and demonstrate EBOV placental tissue tropism indicating potential horizontal and vertical transmission between conspecifics.
- S. A. Riesle-Sbarbaro
- , G. Wibbelt
- & A. Kurth
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Article
| Open AccessIdentification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections
Host factors involved in filovirus infection are incompletely understood. Here, the authors used a haploid cell screening system to unveil CCZ1’s crucial role in regulating endosomal trafficking thus virus movement within cells and thereby impacting Marburg and Ebola infection.
- Vanessa Monteil
- , Hyesoo Kwon
- & Ali Mirazimi
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Article
| Open AccessSpatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories
Here, the authors characterized the phase separation properties and internal structures of intracellular viral factories induced by Ebola virus and correlated these properties to important steps of viral biogenesis.
- Jingru Fang
- , Guillaume Castillon
- & Erica Ollmann Saphire
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Article
| Open AccessSingle-cell profiling of lncRNA expression during Ebola virus infection in rhesus macaques
Long non-coding RNAs (lncRNAs) play key roles in the immune response but their properties at the single-cell level are less well understood. Here, the authors characterize differential features of lncRNAs and protein-coding genes upon Ebola infection in macaques at single-cell resolution.
- Luisa Santus
- , Maria Sopena-Rios
- & Marta Melé
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Article
| Open AccessRNF185 regulates proteostasis in Ebolavirus infection by crosstalk between the calnexin cycle, ERAD, and reticulophagy
Little is known about how proteostasis is maintained during viral infection. Here, the authors identify unexpected crosstalk between the calnexin cycle, ERAD, and reticulophagy, resulting in suppression of ebolavirus glycoprotein expression.
- Jing Zhang
- , Bin Wang
- & Yong-Hui Zheng
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Article
| Open AccessEbola virus VP35 hijacks the PKA-CREB1 pathway for replication and pathogenesis by AKIP1 association
Ebola virus virion protein 35 (VP35) is a cofactor of the viral RNA-dependent RNA polymerase, required for viral assembly and IFN antagonist. Here, Zhu et al. provide evidence that EBOV VP35 induces an AKIP1-mediated (human A kinase interacting protein) activation of the PKA-CREB1 signaling pathway and contributes to viral replication and pathogenesis in vitro and in vivo.
- Lin Zhu
- , Ting Gao
- & Cheng Cao
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Article
| Open AccessStructural insight into Marburg virus nucleoprotein–RNA complex formation
Marburg virus causes severe hemorrhagic fever in humans. Here, the authors determine the structure of Marburg virus nucleoprotein–RNA complex by cryo-electron microscopy and provide mechanistic insight into the helical assembly of the nucleocapsid.
- Yoko Fujita-Fujiharu
- , Yukihiko Sugita
- & Takeshi Noda
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| Open AccessLongitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection
The neurological effects of Ebola disease in the acute stage are not well-described. Here, the authors use longitudinal in vivo neuroimaging and immunohistochemistry to assess pathological changes in the central nervous system in a non-human primate model of Ebola virus infection.
- William Schreiber-Stainthorp
- , Jeffrey Solomon
- & Dima A. Hammoud
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Article
| Open AccessCharacterisation of the T-cell response to Ebola virus glycoprotein amongst survivors of the 2013–16 West Africa epidemic
T cell responses are known to be essential in the immune response to Ebola virus infection, and the viral glycoprotein is a major antigenic target. Here the authors provide fine detail mapping of T cell antigens and their characterisation in Ebola virus survivor patients.
- T. R. W. Tipton
- , Y. Hall
- & M. W. Carroll
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Article
| Open AccessPrior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment
During an ongoing Ebola virus outbreak, infection before onset of protective immunity from vaccination is a possible scenario. Here the authors show in non-human primates that vaccination shortly before treatment with a monoclonal antibody does not negatively affect effectiveness of the antibody therapy.
- Robert W. Cross
- , Zachary A. Bornholdt
- & Thomas W. Geisbert
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Article
| Open AccessIdentification of interferon-stimulated genes that attenuate Ebola virus infection
Here, Kuroda et al. screen a library of nearly 400 interferon-stimulated genes (ISGs) and identify several ISGs that inhibit Ebola virus entry, viral transcription/replication, or virion formation. The study provides insights into interactions between Ebola and the host cells.
- Makoto Kuroda
- , Peter J. Halfmann
- & Yoshihiro Kawaoka
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Article
| Open AccessCross-reactive neutralizing human survivor monoclonal antibody BDBV223 targets the ebolavirus stalk
Human antibodies cross-reactive for several viruses within the Ebolavirus genus have been identified. Here the authors present the crystal structure of such a neutralizing monoclonal antibody (mAb) targeting the stalk of Bundibugyo virus glycoprotein and show that mAb binding may interfere with trimeric bundle assembly and/or the viral membrane.
- Liam B. King
- , Brandyn R. West
- & Erica Ollmann Saphire
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Article
| Open AccessA genome-wide CRISPR screen identifies N-acetylglucosamine-1-phosphate transferase as a potential antiviral target for Ebola virus
Genetic screens are important tools to identify host factors associated with viral infections. Here, Flint et al. perform a genome-wide CRISPR screen using infectious Ebola virus (EBOV) and show that the host transferase GNPTAB is required for EBOV infection and a potential target for antiviral therapies
- Mike Flint
- , Payel Chatterjee
- & Christina F. Spiropoulou
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Article
| Open AccessPost-exposure immunotherapy for two ebolaviruses and Marburg virus in nonhuman primates
Current experimental monoclonal antibodies (mAbs) for Ebola virus (EBOV) post-exposure immunotherapy are ineffective against Sudan (SUDV) or Marburg virus (MARV). Here, authors develop cocktails of mAbs that protect nonhuman primates against EBOV, SUDV, and MARV infection when given four days post infection.
- Jennifer M. Brannan
- , Shihua He
- & M. Javad Aman
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Article
| Open AccessStructural basis for broad neutralization of ebolaviruses by an antibody targeting the glycoprotein fusion loop
The Ebola virus glycoprotein is a target for cross-protective antibodies. Here, Janus et al. report the crystal structure of the antigen-binding fragment of a pan-reactive antibody bound to a conserved epitope of the glycoprotein, facilitating rational design of cross-protective vaccines and therapeutics.
- Benjamin M. Janus
- , Nydia van Dyk
- & Gilad Ofek
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Article
| Open AccessPhylodynamic assessment of intervention strategies for the West African Ebola virus outbreak
During the last Ebola virus outbreak in West Africa, a large amount of viral genomic data was obtained. Here, Dellicour et al. use phylodynamic approaches to assess effect of intervention strategies such as border closures.
- Simon Dellicour
- , Guy Baele
- & Philippe Lemey
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Article
| Open AccessEbola virus VP30 and nucleoprotein interactions modulate viral RNA synthesis
Ebola virus (EBOV) VP30 is a multifunctional protein that plays a role in transcription, but molecular details remain unknown. Here, using X-ray crystallography and minigenome assays, Xuet al. define the interaction between VP30 and a portion of NP that is critical for optimal EBOV RNA synthesis.
- Wei Xu
- , Priya Luthra
- & Gaya K. Amarasinghe
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Article
| Open AccessAssessing the contribution of interferon antagonism to the virulence of West African Ebola viruses
Concerns have been raised regarding potential increase in the virulence of the Ebola virus during the current West African outbreak. Here the authors show that the ability to inhibit interferon response, one of the aspects of Ebola virus virulence, does not differ between the prototype Mayinga and isolates from the current outbreak.
- Eric C. Dunham
- , Logan Banadyga
- & Thomas Hoenen
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Inhibition of Ebola virus glycoprotein-mediated cytotoxicity by targeting its transmembrane domain and cholesterol
The GP protein of the Ebola virus is involved in the detachment of infected cells, which eventually leads to vascular leakage and contributes to haemorrhagic fever. Here Hacke et al.show that the membrane-anchored subunit of GP is sufficient to induce cell detachment, and that cholesterol contributes to this process.
- Moritz Hacke
- , Patrik Björkholm
- & Andreas M. Ernst