Rita M Meganck

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Genomewide CRISPR knockout screen identified PLAC8 as an essential factor for SADS-CoVs infection.

Longping V Tse, Ralph S Baric et 15 al.

May 3, 2022 in Proceedings of the National Academy of Sciences of the United States of America
SignificanceA potential outbreak of swine acute diarrhea syndrome coronavirus (SADS-CoV) in the human population could be devastating. Using genomewide CRISPR knockout screening, we identified the placenta-associated 8 protein (PLAC8) as an essential host factor for SADS-CoV infection, uncovering a novel antiviral target for CoV infection. The PLAC8-related pathway may also have implications for o...


Therapeutic treatment with an oral prodrug of the remdesivir parental nucleoside is protective against SARS-CoV-2 pathogenesis in mice.

Alexandra Schäfer et 28 al.

Mar 22, 2022 in Science translational medicine
The coronavirus disease 2019 (COVID-19) pandemic remains uncontrolled despite the rapid rollout of safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, underscoring the need to develop highly effective antivirals. In the setting of waning immunity from infection and vaccination, breakthrough infections are becoming increasingly common and treatment options rema...


Impact of RNA structure on ZFP36L2 interaction with luteinizing hormone receptor mRNA

Christopher B. Ball et 5 al.

Apr 28, 2017 in RNA
ZFP36L2 (L2) destabilizes AU-rich element (ARE)-containing transcripts and has been implicated in female fertility. We have shown that only one of three putative AREs within the 3` UTR of murine luteinizing hormone receptor mRNA, ARE2197 (UAUUUAU), is capable of interacting with L2. To assess whether structural elements of ARE2197 could explain this unique binding ability, we performed whole-trans...

Tissue-dependent expression and translation of circular RNAs with recombinant AAV vectors in vivo

Rita M. Meganck et 7 al.

Aug 1, 2018 in Molecular Therapy - Nucleic Acids
Circular RNAs (circRNAs) are long-lived, covalently closed RNAs that are abundantly expressed and evolutionarily conserved across eukaryotes. Possible functions ranging from microRNA (miRNA) and RNA binding protein sponges to regulators of transcription and translation have been proposed. Here we describe the design and characterization of recombinant adeno-associated viral (AAV) vectors packaging...


Mapping and Engineering Functional Domains of the Assembly Activating Protein of Adeno-Associated Viruses

Longping V. Tse et 4 al.

Apr 25, 2018 in Journal of Virology
ABSTRACT Adeno-associated viruses (AAVs) encode a unique assembly-activating protein (AAP) within their genomes that is essential for capsid assembly. Studies to date have focused on establishing the role of AAP as a chaperone that mediates the stability, nucleolar transport, and assembly of AAV capsid proteins. Here, we map structure-function correlates of AAP using secondary structure analysis, ...


Ring finger protein 121 is a potent regulator of adeno-associated viral genome transcription

Victoria J. Madigan et 9 al.

Aug 6, 2019 in PLOS Pathogens
Adeno-associated viruses (AAV) are Dependoparvoviruses that have shown promise as recombinant vectors for gene therapy. While infectious pathways of AAV are well studied, gaps remain in our understanding of host factors affecting vector genome expression. Here, we map the role of ring finger protein 121 (RNF121), an E3 ubiquitin ligase, as a key regulator of AAV genome transcription. CRISPR-mediat...


A live dengue virus vaccine carrying a chimeric envelope glycoprotein elicits dual DENV2-DENV4 serotype-specific immunity.

Ellen Young, Ralph S Baric et 18 al.

Mar 13, 2023 in Nature communications
The four dengue virus serotypes co-circulate globally and cause significant human disease. Dengue vaccine development is challenging because some virus-specific antibodies are protective, while others are implicated in enhanced viral replication and more severe disease. Current dengue tetravalent vaccines contain four live attenuated serotypes formulated to theoretically induce balanced protective...

Positive-strand RNA viruses-a Keystone Symposia report.

Jennifer Cable et 45 al.

Jan 25, 2023 in Annals of the New York Academy of Sciences
Positive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic. On June 18-22, 2022, researchers focusing on positive-strand RNA viruses met for the Keystone Symposium "Positive-Strand RNA Viruses" to share the latest research in molecular and cell biology, virology...


Developing therapeutic approaches for twenty-first-century emerging infectious viral diseases.

Rita M Meganck, Ralph S Baric

Mar 15, 2021 in Nature medicine
The twenty-first century has already recorded more than ten major epidemic or pandemic virus emergence events, including the ongoing and devastating coronavirus disease 2019 (COVID-19) pandemic. As viral disease emergence is expected to accelerate, these data dictate a need for proactive approaches to develop broadly active family-specific and cross-family therapeutics for use in future disease ou...