EBOV

Ebola virus (EBOV) infection is threatening human health, especially in Central and West Africa. Limited clinical trials and the requirement of biosafety level-4 laboratories hinder experimental work to advance our understanding of EBOV and the evaluation of treatment. In this work, we use a computational model to study the assembly and budding process of EBOV and evaluate the effect of fendiline on these processes in the context of fluctuating host membrane lipid levels. Our results demonstrate for the first time that the assembly of VP40 filaments may follow the nucleation-elongation theory, as this mechanism is critical to maintaining a pool of VP40 dimers for the maturation and production of virus-like particles (VLPs)...

Single-virus tracking provides a powerful tool for studying virus infection with high spatiotemporal resolution. Quantum dots (QDs) are used to label and track viral particles due to their brightness and photostability. However, labeling viral particles with QDs is not easy. We developed a new method for labeling viral particles with QDs by using the Strep-tag II/streptavidin system. In this method, QDs were site-specifically ligated to viral proteins in live cells and then packaged into viral-like particles (VLPs) of tick-borne encephalitis virus (TBEV) and Ebola virus during viral assembly...

Orthohantaviruses may cause hemorrhagic fever with renal syndrome or hantavirus cardiopulmonary syndrome. Andes virus (ANDV) is the only orthohantavirus associated with human-human transmission. Therefore, emergency vaccination would be a valuable public health measure to combat ANDV-derived infection clusters. Here, we utilized a promising vesicular stomatitis virus (VSV)-based vaccine to advance the approach for emergency applications. We compared monovalent and bivalent VSV vectors containing the Ebola virus (EBOV), glycoprotein (GP), and ANDV glycoprotein precursor (GPC) for protective efficacy in pre-, peri- and post-exposure immunization by the intraperitoneal and intranasal routes...

The interaction of host and Ebola virus (EBOV) proteins is required for establishing infection of the cell. To identify protein binding partners, a proximity-dependent protein interaction screen was performed for six EBOV proteins. Hits were computationally mapped onto a human protein-protein interactome and then annotated with viral proteins to reveal known and previously undescribed EBOV-host protein interactions and processes. Importantly, this approach efficiently arranged proteins into functional complexes associated with single viral proteins...

Ebola virus (EBOV) is a filamentous negative-sense RNA virus which causes severe hemorrhagic fever. There are limited vaccines or therapeutics for prevention and treatment of EBOV, so it is important to get a detailed understanding of the virus lifecycle to illuminate new drug targets. EBOV encodes for the matrix protein, VP40, which regulates assembly and budding of new virions from the inner leaflet of the host cell plasma membrane (PM). In this work we determine the effects of VP40 mutations altering electrostatics on PM interactions and subsequent budding...

The Ebola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from orthoebolavirus zairense (EBOV)-one of three orthoebolavirus species that have caused previous outbreaks. Ebola virus glycoprotein GP mediates viral infection and serves as the primary target of neutralizing antibodies...

Ebola (EBOV) and Marburg (MARV) viruses cause hemorrhagic fever disease in humans and non-human primates (NHPs) with case-fatality rates as high as 90%. The 2013-2016 Ebola virus disease (EVD) outbreak led to over 28,000 cases and 11,000 deaths and took an enormous toll on the economy of West African nations, in the absence of any vaccine or therapeutic options. Like EVD, there have been at least 6 outbreaks of MVD with ~88% case-fatality and the most recent cases emerging in Equatorial Guinea in February 2023...

Ebola virus disease (EVD) caused by Ebola virus (EBOV) is a severe, often fatal, hemorrhagic disease. A critical component of the public health response to curb EVD epidemics is the use of a replication-competent, recombinant vesicular stomatitis virus (rVSV)-vectored Ebola vaccine, rVSVΔG-ZEBOV-GP (ERVEBO). In this Gem, we will discuss the past and ongoing development of rVSVΔG-ZEBOV-GP, highlighting the importance of basic science and the strength of public-private partnerships to translate fundamental virology into a licensed VSV-vectored Ebola vaccine...

Membrane-associated RING-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes. Previous work showed that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates that human MARCH1 and MARCH2 share a similar pattern to MARCH8 in restricting EBOV GP-pseudotyped viral infection. Human MARCH1 and MARCH2 retain EBOV GP at the trans-Golgi network, reduce its cell surface display, and impair EBOV GP-pseudotyped virions infectivity...

The natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles...

Ebolavirus (EBOV) causes severe hemorrhagic fever in humans and is lethal in a large percentage of those infected. The EBOV matrix protein VP40 is a peripheral binding protein that forms a shell beneath the lipid bilayer in virions and virus-like particles (VLPs). VP40 is required for virus assembly and budding from the host cell plasma membrane. VP40 is a dimer that can rearrange into oligomers at the plasma membrane interface, but it is unclear how these structures form and how they are stabilized. We therefore investigated the ability of VP40 to form stable oligomers using in vitro and cellular assays...

Viral inclusion bodies (IBs) commonly form during the replication of Ebola virus (EBOV) in infected cells, but their role in viral immune evasion has rarely been explored. Here, we found that interferon regulatory factor 3 (IRF3), but not TANK-binding kinase 1 (TBK1) or IκB kinase epsilon (IKKε), was recruited and sequestered in viral IBs when the cells were infected by EBOV transcription- and replication-competent virus-like particles (trVLPs). Nucleoprotein/virion protein 35 (VP35)-induced IBs formation was critical for IRF3 recruitment and sequestration, probably through interaction with STING...

BACKGROUND: Ebola virus (EBOV) is a genus of negative-strand RNA viruses belonging to the family Filoviradae that was first described in 1976 in the present-day Democratic Republic of the Congo. It has intermittently affected substantial human populations in West Africa and presents itself as a global health menace due to the high mortality rate of patients, high transmission rate, difficult patient management, and the emergence of complicated autoimmune disease-like conditions post-infection...

As the high pathogenic species of Filoviridae virus family, Orthoebolavirus zairense (EBOV) shows frequent outbreaks in human in recently years since its first emerging in 1976 in Democratic Republic of the Congo (COD), bringing ongoing risks and burden on public health safety. Here, the phylogenetic relationship among major outbreaks was analyzed. The results showed that EBOV isolates could be divided into four lineages according to spatial and temporal epidemics. Then, the positive selection sites (PSS) were detected on all proteins of the EBOV, exhibiting lineage characteristic...

Ebola virus disease (EVD) causes outbreaks and epidemics in West Africa that persist until today. The envelope glycoprotein of Ebola virus (GP) consists of two subunits, GP1 and GP2, and plays a key role in anchoring or fusing the virus to the host cell in its active form on the virion surface. Toremifene (TOR) is a ligand that mainly acts as an estrogen receptor antagonist; however, a recent study showed a strong and efficient interaction with GP. In this context, we aimed to evaluate the energetic affinity features involved in the interaction between GP and toremifene by computer simulation techniques using the Molecular Fractionation Method with Conjugate Caps (MFCC) scheme and quantum-mechanical (QM) calculations, as well as missense mutations to assess protein stability...

Health emergencies caused by epidemic-prone pathogens (EPPs) have increased exponentially in recent decades. Although vaccines have proven beneficial, they are unavailable for many pathogens. Furthermore, achieving timely and equitable access to vaccines against EPPs is not trivial. It requires decision-makers to capture numerous interrelated factors across temporal and spatial scales, with significant uncertainties, variability, delays, and feedback loops that give rise to dynamic and unexpected behavior. Therefore, despite progress in filling R&D gaps, the path to licensure and the long-term viability of vaccines against EPPs continues to be unclear...

In 1976 Ebola revealed itself to the world, marking the beginning of a series of localized outbreaks. However, it was the Ebola outbreak that began in 2013 that incited fear and anxiety around the globe. Since then, our comprehension of the virus has been steadily expanding. Ebola virus (EBOV), belonging to the Orthoebolavirus genus of the Filoviridae family, possesses a non-segmented, negative single-stranded RNA genome comprising seven genes that encode multiple proteins. These proteins collectively orchestrate the intricate process of infecting host cells...

Ebola viral disease (EVD) is a highly infectious and potentially fatal illness with a case fatality rate ranging from 25% to 90%. To effectively control its spread, there is a need for rapid, reliable and lowcost point-of-care (P OC) diagnostic tests. While various EVD diagnostic tests exist, few are P OC tests, and many are not cost-effective. The use of antibodies in these tests has limitations, prompting the exploration of aptamers as potential alternatives. Various proteins from the Ebola virus (EBOV) proteome, including EBOV nucleoprotein (NP), are considered viable targets for diagnostic assays...

UNLABELLED: Human movement drives the transmission and spread of communicable pathogens. It is especially influential for emerging pathogens when population immunity is low and spillover events are rare. We digitized serial printed maps to measure transportation networks (roads and rivers) in Central and West Africa as proxies for population mobility to assess relationships between movement and Ebola transmission. We find that the lengths of roads and rivers in close proximity to spillover sites at or near the time of spillover events are significantly correlated with the number of EVD cases, particularly in the first 100 days of each outbreak...

Monoclonal antibodies (mAbs) against Ebola virus (EBOV) glycoprotein (GP 1,2 ) are the standard of care for Ebola virus disease (EVD). Anti-GP 1,2 mAbs targeting the stalk and membrane proximal external region (MPER) potently neutralize EBOV in vitro . However, their neutralization mechanism is poorly understood because they target a GP 1,2 epitope that has evaded structural characterization. Moreover, their in vivo efficacy has only been evaluated in the mouse model of EVD. Using x-ray crystallography and cryo-electron tomography of 3A6 complexed with its stalk- GP 1,2 MPER epitope we reveal a novel mechanism in which 3A6 elevates the stalk or stabilizes a conformation of GP 1,2 that is lifted from the virion membrane...