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The 2014 outbreak of Ebola virus caused more than 10,000 human deaths. Current knowledge of suitable drugs, clinical diagnostic biomarkers and molecular mechanisms of Ebola virus infection is either absent or insufficient. By screening stem-loop structures from the viral genomes of four virulence species, we identified a novel, putative viral microRNA precursor that is specifically expressed by the Ebola virus. The sequence of the microRNA precursor was further confirmed by mining the existing RNA-Seq database. Two putative mature microRNAs were predicted and subsequently validated in human cell lines. Combined with this prediction of the microRNA target, we identified importin- alpha 5, which is a key regulator of interferon signaling following Ebola virus infection, as one putative target. We speculate that this microRNA could facilitate the evasion of the host immune system by the virus. Moreover, this microRNA might be a potential clinical therapeutic target or a diagnostic biomarker for Ebola virus.

In March 2014, an outbreak of Ebola virus disease associated with a high fatality rate was identified in Guinea, with evidence of ongoing person-to-person transmission. In this update to the preliminary report, the virus is found to be a new strain related to Zaire ebolavirus . Outbreaks caused by viruses of the genera ebolavirus and marburgvirus represent a major public health issue in sub-Saharan Africa. Ebola virus disease is associated with a case fatality rate of 30 to 90%, depending on the virus species. Specific conditions in hospitals and communities in Africa facilitate the spread of the disease from human to human. Three ebolavirus species have caused large outbreaks in sub-Saharan Africa: EBOV, Sudan ebolavirus, and the recently described Bundibugyo ebolavirus . 1 , 2 Epidemics have occurred in the Democratic Republic of Congo, Sudan, Gabon, Republic of Congo, and Uganda. Reston ebolavirus circulates in the Philippines. It . . .

A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. Ebola virus genomics surveillance This paper reports the use of nanopore DNA sequencers (known as MinIONs) for real-time genomic surveillance of the Ebola virus epidemic, in the field in Guinea. The authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths 1 . Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10 −3 and 1.42 × 10 −3 mutations per site per year. This is equivalent to 16–27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic 2 , 3 , 4 , 5 , 6 , 7 . Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions 8 . Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities 9 . To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15–60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

This final report updates preliminary data on an attenuated, replication-competent, recombinant vesicular stomatitis virus–based vaccine candidate designed to prevent Ebola virus disease. The results supported the safety and immunogenicity of up to two doses of the vaccine. The worst Ebola virus disease (EVD) outbreak in recorded history has resulted in more than 28,000 cases and 11,000 reported deaths. 1 Although the primary strategy to stop the transmission of Ebola remains the identification and isolation of contacts and the use of appropriate personal protective equipment, the development of a safe and efficacious vaccine would provide an important public health tool. Numerous Ebola virus vaccine candidates are in preclinical development, and some have proceeded to human trials. 2 – 5 An Ebola virus vaccine candidate based on an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV) has shown promise in preclinical studies. The . . .

The Ebola virus (EBOV) envelope glycoprotein (GP) is a membrane fusion machine required for virus entry into cells. Following endocytosis of EBOV, the GP1 domain is cleaved by cellular cathepsins in acidic endosomes, removing the glycan cap and exposing a binding site for the Niemann-Pick C1 (NPC1) receptor. NPC1 binding to cleaved GP1 is required for entry. How this interaction translates to GP2 domain-mediated fusion of viral and endosomal membranes is not known. Here, using a bulk fluorescence dequenching assay and single-molecule Förster resonance energy transfer (smFRET)-imaging, we found that acidic pH, Ca2+, and NPC1 binding synergistically induce conformational changes in GP2 and permit virus-liposome lipid mixing. Acidic pH and Ca2+ shifted the GP2 conformational equilibrium in favor of an intermediate state primed for NPC1 binding. Glycan cap cleavage on GP1 enabled GP2 to transition from a reversible intermediate to an irreversible conformation, suggestive of the postfusion 6-helix bundle; NPC1 binding further promoted transition to the irreversible conformation. Thus, the glycan cap of GP1 may allosterically protect against inactivation of EBOV by premature triggering of GP2.

The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2‐year‐old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in a hollow tree housing a colony of insectivorous free‐tailed bats ( Mops condylurus ). Bats in this family have previously been discussed as potential sources for Ebola virus outbreaks, and experimental data have shown that this species can survive experimental infection. These analyses expand the range of possible Ebola virus sources to include insectivorous bats and reiterate the importance of broader sampling efforts for understanding Ebola virus ecology. Synopsis The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2‐year‐old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free‐tailed bats living in a nearby hollow tree. Monitoring data show that larger wildlife did not experience a recent decline and is therefore unlikely to have served as the source for the Ebola virus disease epidemic in West Africa. Fruit bat hunting and butchering are common activities in southern Guinea, therefore facilitating direct human contact. Children are also exposed to insectivorous bats through hunting in and around villages. No large colony of fruit bats exists in or nearby the index village (Meliandou). The 2‐year‐old index case may have been infected by playing in a hollow tree housing a colony of insectivorous free‐tailed bats ( Mops condylurus ). Graphical Abstract The severe Ebola virus disease epidemic occurring in West Africa likely stems from a single zoonotic transmission event involving a 2‐year‐old boy in Meliandou, Guinea, who might have been infected by hunting or playing with insectivorous free‐tailed bats living in a nearby hollow tree.

To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-s activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN [Beta]-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN [Beta]-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit. Cognizant of the limitations of having treated only 9 individuals with EVD, the data collected are cautiously considered. When compared to supportive care only, IFN [Beta]-1a treatment seemed to facilitate viral clearance from the blood and appeared associated with earlier resolution of disease symptoms. Survival, calculated from the date of consent for those in the trial and date of admission from those in the control cohort, to the date of death, was 19% for those receiving supportive care only, compared to 67% for those receiving supportive care plus IFN [Beta]-1a. Given the differences in baseline blood viremia between the control cohort and the IFN-treated cohort, an additional 17 controls were included for a subset analysis, from other treatment units in Guinea, matched with the IFN-treated patients based on age and baseline blood viremia. Subset analyses using this expanded control cohort suggests that patients without IFN [Beta]-1a treatment were ~ 1.5-1.9 fold more likely to die than those treated. Viewed altogether the results suggest a rationale for further clinical evaluation of IFN [Beta]-1a.

The Ebola virus, a member of the Filoviridae family, causes severe hemorrhagic fever in humans. Filamentous virions contain a helical nucleocapsid responsible for genome transcription, replication, and packaging into progeny virions. The nucleocapsid consists of a helical nucleoprotein (NP)–viral genomic RNA complex forming the core structure, to which VP24 and VP35 bind externally. Two NPs, each paired with a VP24 molecule, constitute a repeating unit. However, the detailed nucleocapsid structure remains unclear. Here, we determine the nucleocapsid-like structure within virus-like particles at 4.6 Å resolution using single-particle cryo-electron microscopy. Mutational analysis identifies specific interactions between the two NPs and two VP24s and demonstrates that each of the two VP24s in different orientations distinctively regulates nucleocapsid assembly, viral RNA synthesis, intracellular transport of the nucleocapsid, and infectious virion production. Our findings highlight the sophisticated mechanisms underlying the assembly and functional regulation of the nucleocapsid and provide insights into antiviral development. Here, the authors use cryo-electron microscopy to structurally characterise the Ebola virus nucleocapsid within virus-like particles, uncovering how specific interactions regulate viral genome synthesis, assembly, and infectious particle production.

The 2013–2016 Ebola virus (EBOV) disease epidemic demonstrated the grave consequences of filovirus epidemics in the absence of effective therapeutics. Besides EBOV, two additional ebolaviruses, Sudan (SUDV) and Bundibugyo (BDBV) viruses, as well as multiple variants of Marburg virus (MARV), have also caused high fatality epidemics. Current experimental EBOV monoclonal antibodies (mAbs) are ineffective against SUDV, BDBV, or MARV. Here, we report that a cocktail of two broadly neutralizing ebolavirus mAbs, FVM04 and CA45, protects nonhuman primates (NHPs) against EBOV and SUDV infection when delivered four days post infection. This cocktail when supplemented by the anti-MARV mAb MR191 exhibited 100% efficacy in MARV-infected NHPs. These findings provide a solid foundation for clinical development of broadly protective immunotherapeutics for use in future filovirus epidemics. 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.