A zebrafish-based in vivo model of Zika virus infection unveils alterations of the glutamatergic neuronal development and NS4A as a key viral determinant of neuropathogenesis.

Infection of pregnant women by Zika virus (ZIKV) is associated with severe neurodevelopmental defects in newborns through poorly defined mechanisms. Here, we established a zebrafish in vivo model of ZIKV infection to circumvent limitations of existing mammalian models. Leveraging the unique tractability of this system, we gained unprecedented access to the ZIKV-infected brain at early developmental stages.

Zika virus remodels and hijacks IGF2BP2 ribonucleoprotein complex to promote viral replication organelle biogenesis.

Zika virus (ZIKV) infection causes significant human disease that, with no approved treatment or vaccine, constitutes a major public health concern. Its life cycle entirely relies on the cytoplasmic fate of the viral RNA genome (vRNA) through a fine-tuned equilibrium between vRNA translation, replication, and packaging into new virions, all within virus-induced replication organelles (vROs). In this study, with an RNA interference (RNAi) mini-screening and subsequent functional characterization, we have identified insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) as a new host dependency factor that regulates vRNA synthesis.

Rapid On-Site Detection of Arboviruses by a Direct RT-qPCR Assay.

Arthropod-borne diseases currently constitute a source of major health concerns worldwide. They account for about 50% of global infectious diseases and cause nearly 700,000 deaths every year. Their rapid increase and spread constitute a huge challenge for public health, highlighting the need for early detection during epidemics, to curtail the virus spread, and to enhance outbreak management.

COVID-19 in 16 West African Countries: An Assessment of the Epidemiology and Genetic Diversity of SARS-CoV-2 after Four Epidemic Waves.

West Africa faced the COVID-19 pandemic in early March 2020 and, as of March 31, 2022, had more than 900,000 confirmed cases and more than 12,000 deaths. During this period, SARS-CoV-2 genomes evolved genetically, resulting in the emergence of distinct lineages. This review was conducted to provide the epidemiological profile of COVID-19, the mutational profile of SARS-CoV-2, and the dynamics of its lineages in the 16 west African countries by analyzing data from 33 studies and seven situation reports.

N-Phenylpyridine-3-Carboxamide and 6-Acetyl-1H-Indazole Inhibit the RNA Replication Step of the Dengue Virus Life Cycle.

Dengue virus (DENV) is a that causes the most prevalent arthropod-borne viral disease. Clinical manifestation of DENV infection ranges from asymptomatic to severe symptoms that can lead to death. Unfortunately, no antiviral treatments against DENV are currently available.

Fragment-Based Phenotypic Lead Discovery To Identify New Drug Seeds That Target Infectious Diseases.

Fragment-based lead discovery has emerged over the last decades as one of the most powerful techniques for identifying starting chemical matter to target specific proteins or nucleic acids . However, the use of such low-molecular-weight fragment molecules in cell-based phenotypic assays has been historically avoided because of concerns that bioassays would be insufficiently sensitive to detect the limited potency expected for such small molecules and that the high concentrations required would likely implicate undesirable artifacts. Herein, we applied phenotype cell-based screens using a curated fragment library to identify inhibitors against a range of pathogens including , , , , and flaviviruses.

The Biogenesis of Dengue Virus Replication Organelles Requires the ATPase Activity of Valosin-Containing Protein.

The dengue virus (DENV) causes the most prevalent arthropod-borne viral disease worldwide. While its incidence is increasing in many countries, there is no approved antiviral therapy currently available. In infected cells, the DENV induces extensive morphological alterations of the endoplasmic reticulum (ER) to generate viral replication organelles (vRO), which include convoluted membranes (CM) and vesicle packets (VP) hosting viral RNA replication.

Amaryllidaceae Alkaloid Cherylline Inhibits the Replication of Dengue and Zika Viruses.

Dengue fever, caused by dengue virus (DENV), is the most prevalent arthropod-borne viral disease and is endemic in many tropical and subtropical parts of the world, with an increasing incidence in temperate regions. The closely related flavivirus Zika virus (ZIKV) can be transmitted vertically and causes congenital Zika syndrome and other birth defects. In adults, ZIKV is associated with Guillain-Barré syndrome.

Valosin-containing protein ATPase activity regulates the morphogenesis of Zika virus replication organelles and virus-induced cell death.

With no available therapies, infections with Zika virus (ZIKV) constitute a major public health concern as they can lead to congenital microcephaly. In order to generate an intracellular environment favourable to viral replication, ZIKV induces endomembrane remodelling and the morphogenesis of replication factories via enigmatic mechanisms. In this study, we identified the AAA+ type ATPase valosin-containing protein (VCP) as a cellular interaction partner of ZIKV non-structural protein 4B (NS4B).

Very-long-chain fatty acid metabolic capacity of 17-beta-hydroxysteroid dehydrogenase type 12 (HSD17B12) promotes replication of hepatitis C virus and related flaviviruses.

Flaviviridae infections represent a major global health burden. By deciphering mechanistic aspects of hepatitis C virus (HCV)-host interactions, one could discover common strategy for inhibiting the replication of related flaviviruses. By elucidating the HCV interactome, we identified the 17-beta-hydroxysteroid dehydrogenase type 12 (HSD17B12) as a human hub of the very-long-chain fatty acid (VLCFA) synthesis pathway and core interactor.

The Interplay between Dengue Virus and the Human Innate Immune System: A Game of Hide and Seek.

With 40% of the world population at risk, infections with dengue virus (DENV) constitute a serious threat to public health. While there is no antiviral therapy available against this potentially lethal disease, the efficacy of the only approved vaccine is not optimal and its safety has been recently questioned. In order to develop better vaccines based on attenuated and/or chimeric viruses, one must consider how the human immune system is engaged during DENV infection.