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  1. Article ; Online: Lung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection

    Ning Yang / Joseph M. Luna / Peihong Dai / Yi Wang / Charles M. Rice / Liang Deng

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 17

    Abstract: Smallpox is a highly contagious respiratory pathogen associated with a high mortality rate. Here the authors utilize a mouse model of intranasal vaccinia virus infection and show a C7 gene encoded virulence factor attenuates type I IFN release by lung ... ...

    Abstract Smallpox is a highly contagious respiratory pathogen associated with a high mortality rate. Here the authors utilize a mouse model of intranasal vaccinia virus infection and show a C7 gene encoded virulence factor attenuates type I IFN release by lung type II alveolar epithelial cells and reduces lung inflammatory monocyte responses.
    Keywords Science ; Q
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Author Correction

    Kathryn Rozen-Gagnon / Soon Yi / Eliana Jacobson / Sasha Novack / Charles M. Rice

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    A selectable, plasmid-based system to generate CRISPR/Cas9 gene edited and knock-in mosquito cell lines

    2021  Volume 1

    Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A selectable, plasmid-based system to generate CRISPR/Cas9 gene edited and knock-in mosquito cell lines

    Kathryn Rozen-Gagnon / Soon Yi / Eliana Jacobson / Sasha Novack / Charles M. Rice

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 14

    Abstract: Abstract Aedes (Ae.) aegypti and Ae. albopictus mosquitoes transmit arthropod-borne diseases around the globe, causing ~ 700,000 deaths each year. Genetic mutants are valuable tools to interrogate both fundamental vector biology and mosquito host factors ...

    Abstract Abstract Aedes (Ae.) aegypti and Ae. albopictus mosquitoes transmit arthropod-borne diseases around the globe, causing ~ 700,000 deaths each year. Genetic mutants are valuable tools to interrogate both fundamental vector biology and mosquito host factors important for viral infection. However, very few genetic mutants have been described in mosquitoes in comparison to model organisms. The relative ease of applying CRISPR/Cas9-based gene editing has transformed genome engineering and has rapidly increased the number of available gene mutants in mosquitoes. Yet, in vivo studies may not be practical for screening large sets of mutants or possible for laboratories that lack insectaries. Thus, it would be useful to adapt CRISPR/Cas9 systems to common mosquito cell lines. In this study, we generated and characterized a mosquito optimized, plasmid-based CRISPR/Cas9 system for use in U4.4 (Ae. albopictus) and Aag2 (Ae. aegypti) cell lines. We demonstrated highly efficient editing of the AGO1 locus and isolated U4.4 and Aag2 cell lines with reduced AGO1 expression. Further, we used homology-directed repair to establish knock-in Aag2 cell lines with a 3xFLAG-tag at the N-terminus of endogenous AGO1. These experimentally verified plasmids are versatile, cost-effective, and efficiently edit immune competent mosquito cell lines that are widely used in arbovirus studies.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The HLA-II immunopeptidome of SARS-CoV-2

    Shira Weingarten-Gabbay / Da-Yuan Chen / Siranush Sarkizova / Hannah B. Taylor / Matteo Gentili / Gabrielle M. Hernandez / Leah R. Pearlman / Matthew R. Bauer / Charles M. Rice / Karl R. Clauser / Nir Hacohen / Steven A. Carr / Jennifer G. Abelin / Mohsan Saeed / Pardis C. Sabeti

    Cell Reports, Vol 43, Iss 1, Pp 113596- (2024)

    1481  

    Abstract: Summary: Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 ...

    Abstract Summary: Targeted synthetic vaccines have the potential to transform our response to viral outbreaks, yet the design of these vaccines requires a comprehensive knowledge of viral immunogens. Here, we report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) peptides that are naturally processed and loaded onto human leukocyte antigen-II (HLA-II) complexes in infected cells. We identify over 500 unique viral peptides from canonical proteins as well as from overlapping internal open reading frames. Most HLA-II peptides colocalize with known CD4+ T cell epitopes in coronavirus disease 2019 patients, including 2 reported immunodominant regions in the SARS-CoV-2 membrane protein. Overall, our analyses show that HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for most of the HLA-II peptidome and nonstructural and noncanonical proteins accounting for the majority of the HLA-I peptidome. These findings highlight the need for a vaccine design that incorporates multiple viral elements harboring CD4+ and CD8+ T cell epitopes to maximize vaccine effectiveness.
    Keywords CP: Microbiology ; CP: Immunology ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model

    Andrew M. Cheung / Elaine Z. Yip / Alison W. Ashbrook / Niluka Goonawardane / Corrine Quirk / Charles M. Rice / Margaret R. MacDonald / Hans-Heinrich Hoffmann

    Vaccines, Vol 11, Iss 612, p

    2023  Volume 612

    Abstract: Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. Here, we took two independent approaches ...

    Abstract Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. Here, we took two independent approaches to develop vaccine candidates. First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease.
    Keywords Powassan virus ; deer tick virus ; live-attenuated vaccine ; yellow fever 17D virus vaccine ; CpG and UpA dinucleotides ; zinc finger antiviral protein (ZAP) ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Author Correction

    Natalia Cheshenko / Jeffrey B. Bonanno / Hans-Heinrich Hoffmann / Rohit K. Jangra / Kartik Chandran / Charles M. Rice / Steven C. Almo / Betsy C. Herold

    Communications Biology, Vol 6, Iss 1, Pp 1-

    Cell-impermeable staurosporine analog targets extracellular kinases to inhibit HSV and SARS-CoV-2

    2023  Volume 1

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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  7. Article: Getting Rid of a Persistent Troublemaker to Cure Hepatitis

    Shlomai, Amir / Charles M. Rice

    Science. 2014 Mar. 14, v. 343, no. 6176

    2014  

    Abstract: One of the major enigmas in hepatitis B virus (HBV) infection is the striking persistence of its episomal DNA [covalently closed circular DNA (cccDNA)], the viral transcriptional template sequestered in the nucleus of infected hepatocytes. Eradicating ... ...

    Abstract One of the major enigmas in hepatitis B virus (HBV) infection is the striking persistence of its episomal DNA [covalently closed circular DNA (cccDNA)], the viral transcriptional template sequestered in the nucleus of infected hepatocytes. Eradicating cccDNA is a requisite for virus elimination and cure, a desirable end point for the 400 million people chronically infected by HBV worldwide who are at a substantial risk for end-stage liver disease and liver cancer. Commonly used therapies suppress viral replication, but because they are ineffective at targeting the cccDNA pool, they often require lifelong administration to prevent viral rebound (1). Thus, the development of new drugs that efficiently and specifically target HBV cccDNA is a priority. On page 1221 of this issue, Lucifora et al. (2) uncover a mechanism that destroys cccDNA, which can be activated by two different approaches.
    Keywords circular DNA ; hepatitis ; Hepatitis B virus ; hepatocytes ; liver neoplasms ; new drugs ; people ; risk ; transcription (genetics) ; virus replication ; viruses
    Language English
    Dates of publication 2014-0314
    Size p. 1212-1213.
    Publishing place American Association for the Advancement of Science
    Document type Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.1252186
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals

    Frank J. Piscotta / Hans-Heinrich Hoffmann / Young Joo Choi / Gabriel I. Small / Alison W. Ashbrook / Bimal Koirala / Elizabeth A. Campbell / Seth A. Darst / Charles M. Rice / Sean F. Brady

    mSphere, Vol 6, Iss

    2021  Volume 6

    Abstract: ABSTRACT The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological ... ...

    Abstract ABSTRACT The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored. Using a cell-based SARS-CoV-2 infection assay, we screened culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity. Bioassay-guided fractionation uncovered three bacterial metabolites capable of inhibiting SARS-CoV-2 infection. This included the nucleoside analogue N6-(Δ2-isopentenyl)adenosine, the 5-hydroxytryptamine receptor agonist tryptamine, and the pyrazine 2,5-bis(3-indolylmethyl)pyrazine. The most potent of these, N6-(Δ2-isopentenyl)adenosine, had a 50% inhibitory concentration (IC50) of 2 μM. These natural antiviral compounds exhibit structural and functional similarities to synthetic drugs that have been clinically examined for use against COVID-19. Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections. IMPORTANCE The continued prevalence of COVID-19 and the emergence of new variants has once again put the spotlight on the need for the identification of SARS-CoV-2 antivirals. The human microbiome produces an array of small molecules with bioactivities (e.g., host receptor ligands), but its ability to produce antiviral small molecules is relatively underexplored. Here, using a cell-based screening platform, we describe the isolation of three microbiome-derived metabolites that are able to prevent SARS-CoV-2 infection in vitro. These molecules display structural similarities to ...
    Keywords biochemistry ; molecular biology ; virology ; Microbiology ; QR1-502
    Subject code 572
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher American Society for Microbiology
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Isogenic human trophectoderm cells demonstrate the role of NDUFA4 and associated variants in ZIKV infection

    Liuliu Yang / Yuling Han / Ting Zhou / Lauretta A. Lacko / Mohsan Saeed / Christina Tan / Ron Danziger / Jiajun Zhu / Zeping Zhao / Clare Cahir / Alice Maria Giani / Yang Li / Xue Dong / Dorota Moroziewicz / Daniel Paull / Zhengming Chen / Aaron Zhong / Scott A. Noggle / Charles M. Rice /
    Qibin Qi / Todd Evans / Shuibing Chen

    iScience, Vol 26, Iss 7, Pp 107001- (2023)

    2023  

    Abstract: Summary: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying ... ...

    Abstract Summary: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in NDUFA4, harboring risk versus non-risk alleles of SNPs (rs917172 and rs12386620) or having deletions in the NDUFA4 cis-regulatory region with ZIKV. We found that loss/reduction of NDUFA4 suppressed ZIKV infection in trophectoderm cells. This study validated our published hiPSC array-based system as a useful platform for GWAS and confirmed the role of NDUFA4 as a susceptibility locus for ZIKV in disease-relevant trophectoderm cells.
    Keywords Stem cells research ; Virology ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Identification of a Small Interface between the Methyltransferase and RNA Polymerase of NS5 that is Essential for Zika Virus Replication

    Timur Rusanov / Tatiana Kent / Mohsan Saeed / Trung M. Hoang / Crystal Thomas / Charles M. Rice / Richard T. Pomerantz

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 11

    Abstract: Abstract The spread of Zika virus (ZIKV) has caused an international health emergency due to its ability to cause microcephaly in infants. Yet, our knowledge of how ZIKV replicates at the molecular level is limited. For example, how the non-structural ... ...

    Abstract Abstract The spread of Zika virus (ZIKV) has caused an international health emergency due to its ability to cause microcephaly in infants. Yet, our knowledge of how ZIKV replicates at the molecular level is limited. For example, how the non-structural protein 5 (NS5) performs replication, and in particular whether the N-terminal methytransferase (MTase) domain is essential for the function of the C-terminal RNA-dependent RNA polymerase (RdRp) remains unclear. In contrast to previous reports, we find that MTase is absolutely essential for all activities of RdRp in vitro. For instance, the MTase domain confers stability onto the RdRp elongation complex (EC) and and is required for de novo RNA synthesis and nucleotide incorporation by RdRp. Finally, structure function analyses identify key conserved residues at the MTase-RdRp interface that specifically activate RdRp elongation and are essential for ZIKV replication in Huh-7.5 cells. These data demonstrate the requirement for the MTase-RdRp interface in ZIKV replication and identify a specific site within this region as a potential site for therapeutic development.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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