Filovirus Infection in Humanized Mouse Models.

Since the discovery of filoviruses in 1967, there have been more than 40 outbreaks with high case-fatality rates causing more than 30,000 deaths in humans. Filovirus disease (FVD) involves the dysregulation of many host physiological processes. While many advances in the field have taken place since the first outbreaks, the dearth of small animal models that translate the features observed during FVD in humans has limited our understanding of the pathology.

Ebola Virus Infection of Flt3-Dependent, Conventional Dendritic Cells and Antigen Cross-presentation Leads to High Levels of T-Cell Activation.

Background: Previous studies have described that Ebola virus (EBOV) infection of human monocyte-derived dendritic cells (moDCs) inhibits dendritic cell (DC) maturation, resulting in poor T-cell activation. However, it is unknown how other DC subsets distinct from moDCs respond to EBOV infection.

Methods: To better understand how DCs initiate T-cell activation during EBOV infection, we assessed the response of conventional mouse DCs (cDCs) to EBOV infection utilizing a recombinant EBOV expressing the model antigen ovalbumin.

Intracellular lipid droplets are exploited by Junín virus in a nucleoprotein-dependent process.

Lipid droplets (LDs) are organelles involved in lipid storage, maintenance of energy homeostasis, protein sequestration, signaling events and inter-organelle interactions. Recently, LDs have been shown to favor the replication of members from different viral families, such as the Flaviviridae and Coronaviridae. In this work, we show that LDs are essential organelles for members of the Arenaviridae family.

Discovery of Thiophene Derivatives as Potent, Orally Bioavailable, and Blood-Brain Barrier-Permeable Ebola Virus Entry Inhibitors.

The endemic nature of the Ebola virus disease in Africa underscores the need for prophylactic and therapeutic drugs that are affordable and easy to administer. Through a phenotypic screening employing viral pseudotypes and our in-house chemical library, we identified a promising hit featuring a thiophene scaffold, exhibiting antiviral activity in the micromolar range. Following up on this thiophene hit, a new series of compounds that retain the five-membered heterocyclic scaffold while modifying several substituents was synthesized.

'-Phenylacetohydrazide Derivatives as Potent Ebola Virus Entry Inhibitors with an Improved Pharmacokinetic Profile.

Ebola virus (EBOV) is a single-strand RNA virus belonging to the family, which has been associated to most Ebola virus disease outbreaks to date, including the West African and the North Kivu epidemics between 2013 and 2022. This unprecedented health emergency prompted the search for effective medical countermeasures. Following up on the carbazole hit identified in our previous studies, we synthetized a new series of compounds, which demonstrated to prevent EBOV infection in cells by acting as virus entry inhibitors.

Use of Hu-PBL Mice to Study Pathogenesis of Human-Restricted Viruses.

Different humanized mouse models have been developed to study human diseases such as autoimmune illnesses, cancer and viral infections. These models are based on the use of immunodeficient mouse strains that are transplanted with human tissues or human immune cells. Among the latter, mice transplanted with hematopoietic stem cells have been widely used to study human infectious diseases.

Animal Model Alternatives in Filovirus and Bornavirus Research.

The order contains a variety of highly pathogenic viruses that may infect humans, including the families , , , and . Animal models have historically been important to study virus pathogenicity and to develop medical countermeasures. As these have inherent shortcomings, the rise of microphysiological systems and organoids able to recapitulate hallmarks of the diseases caused by these viruses may have enormous potential to add to or partially replace animal modeling in the future.

Avatar Mice Underscore the Role of the T Cell-Dendritic Cell Crosstalk in Ebola Virus Disease and Reveal Mechanisms of Protection in Survivors.

Ebola virus disease (EVD) is a complex infectious disease characterized by high inflammation, multiorgan failure, the dysregulation of innate and adaptive immune responses, and coagulation abnormalities. Evidence accumulated over the last 2 decades indicates that, during fatal EVD, the infection of antigen-presenting cells (APC) and the dysregulation of T cell immunity preclude a successful transition between innate and adaptive immunity, which constitutes a key disease checkpoint. In order to better understand the contribution of the APC-T cell crosstalk to EVD pathophysiology, we have developed avatar mice transplanted with human, donor-specific APCs and T cells.

A platform trial design for preventive vaccines against Marburg virus and other emerging infectious disease threats.

Background: The threat of a possible Marburg virus disease outbreak in Central and Western Africa is growing. While no Marburg virus vaccines are currently available for use, several candidates are in the pipeline. Building on knowledge and experiences in the designs of vaccine efficacy trials against other pathogens, including SARS-CoV-2, we develop designs of randomized Phase 3 vaccine efficacy trials for Marburg virus vaccines.

Zaire ebolavirus surveillance near the Bikoro region of the Democratic Republic of the Congo during the 2018 outbreak reveals presence of seropositive bats.

On the 8th of May, 2018, an outbreak of Ebola virus disease (EVD) was declared, originating in the Bikoro region of the Democratic Republic of the Congo (DRC) near the border with neighboring Republic of the Congo (ROC). Frequent trade and migration occur between DRC and ROC-based communities residing along the Congo River. In June 2018, a field team was deployed to determine whether Zaire ebolavirus (Ebola virus (EBOV)) was contemporaneously circulating in local bats at the human-animal interface in ROC near the Bikoro EVD outbreak.

Inactivation Methods for Experimental Nipah Virus Infection.

Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe disease in humans and livestock. Due to its high pathogenicity in humans and the lack of available vaccines and therapeutics, NiV needs to be handled in biosafety level 4 (BSL-4) laboratories. Safe inactivation of samples containing NiV is thus necessary to allow further processing in lower containment areas.

Quantification of Type I Interferon Inhibition by Viral Proteins: Ebola Virus as a Case Study.

Type I interferons (IFNs) are cytokines with both antiviral properties and protective roles in innate immune responses to viral infection. They induce an antiviral cellular state and link innate and adaptive immune responses. Yet, viruses have evolved different strategies to inhibit such host responses.

SARS-CoV-2 Variants and Vaccines.

Viral variants of concern may emerge with dangerous resistance to the immunity generated by the current vaccines to prevent coronavirus disease 2019 (Covid-19). Moreover, if some variants of concern have increased transmissibility or virulence, the importance of efficient public health measures and vaccination programs will increase. The global response must be both timely and science based.

Development and validation of portable, field-deployable Ebola virus point-of-encounter diagnostic assay for wildlife surveillance.

Unlabelled: Early detection of Ebola virus spillover into wildlife is crucial for rapid response. We developed and validated a portable, cold-chain independent Ebola virus RT-qPCR assay.

Methods: The field syringe-based RNA extraction method was compared with a conventional laboratory-based spin-column RNA extraction method.

Metagenomic Snapshots of Viral Components in Guinean Bats.

To prevent the emergence of zoonotic infectious diseases and reduce their epidemic potential, we need to understand their origins in nature. Bats in the order Chiroptera are widely distributed worldwide and are natural reservoirs of prominent zoonotic viruses, including Nipah virus, Marburg virus, and possibly SARS-CoV-2. In this study, we applied unbiased metagenomic and metatranscriptomic approaches to decipher the virosphere of frugivorous and insectivorous bat species captured in Guéckédou, Guinea, the epicenter of the West African Ebola virus disease epidemic in 2013-2016.

Reduced Nucleoprotein Availability Impairs Negative-Sense RNA Virus Replication and Promotes Host Recognition.

Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent RNA polymerases (RdRp) to replicate and transcribe their viral genomes. Their replication machinery consists of an RdRp bound to viral RNA which is wound around a nucleoprotein (NP) scaffold, forming a viral ribonucleoprotein complex. NSV NP is known to regulate transcription and replication of genomic RNA; however, its role in maintaining and protecting the viral genetic material is unknown.

Factors associated with progression to death in patients with Lassa fever in Nigeria: an observational study.

Background: Lassa fever is endemic in several west African countries. Case-fatality rates ranging from 21% to 69% have been reported. The pathophysiology of the disease in humans and determinants of mortality remain poorly understood.

N-terminal VP1 Truncations Favor = 1 Norovirus-Like Particles.

Noroviruses cause immense sporadic gastroenteritis outbreaks worldwide. Emerging genotypes, which are divided based on the sequence of the major capsid protein VP1, further enhance this public threat. Self-assembling properties of the human norovirus major capsid protein VP1 are crucial for using virus-like particles (VLPs) for vaccine development.