Unlabelled: Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses La Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics.
Importance: RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. These studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.
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http://dx.doi.org/10.1128/JVI.00543-16 | DOI Listing |
World J Gastroenterol
January 2025
Department of Internal Medicine, Mixed Hospital of Laghouat, Laghouat Faculty of Medicine, Amar Telidji University, Laghouat 03000, Algeria.
Liver cancer remains a significant global health challenge, characterized by high incidence and mortality rates. Despite advancements in medical treatments, the prognosis for liver cancer patients remains poor, highlighting the urgent need for novel therapeutic approaches. Traditional Chinese medicine (TCM), particularly (CB), has shown promise in addressing this need due to its multi-target therapeutic mechanisms.
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Pluripotency Dynamics Group, Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064 Russian Federation.
Embryonic stem cells (ESCs) hold great promise for regenerative medicine thanks to their ability to self-renew and differentiate into somatic cells and the germline. ESCs correspond to pluripotent epiblast - the tissue from which the following three germ layers originate during embryonic gastrulation: the ectoderm, mesoderm, and endoderm. Importantly, ESCs can be induced to differentiate toward various cell types by varying culture conditions, which can be exploited for modeling of developmental processes such as gastrulation.
View Article and Find Full Text PDFJ Dent Res
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Odontogenic keratocyst (OKC) and ameloblastoma (AM) are common jaw lesions with high bone-destructive potential and recurrence rates. Recent advancements in technology led to significant progress in understanding these conditions. Single-cell and spatial omics have improved insights into the tumor microenvironment and cellular heterogeneity in OKC and AM.
View Article and Find Full Text PDFSci Rep
January 2025
School of Pharmacy, Division of Pharmaceutical Sciences, University of Wisconsin-Madison, Madison, WI, USA.
The central nervous system (CNS) requires specialized blood vessels to support neural function within specific microenvironments. During neurovascular development, endothelial Wnt/β-catenin signaling is required for BBB development within the brain parenchyma, whereas fenestrated blood vessels that lack BBB properties do not require Wnt/β-catenin signaling. Here, we used zebrafish to further characterize this phenotypic heterogeneity of the CNS vasculature.
View Article and Find Full Text PDFCell Signal
January 2025
Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:
KDELR1, a constituent of the KDEL endoplasmic reticulum protein retention receptors family, is implicated in immune responses and cancers progression. In this study, we delineate the clinicopathological significance and oncogenic role of KDELR1 in head and neck squamous cell carcinoma (HNSCC) through a comprehensive multi-omics approach. KDELR1 expression is correlated with tumor grade, tumor stage, lymph node metastasis, clinical stage and poor prognosis in HNSCC.
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