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  1. Article: Using structure prediction of negative sense RNA virus nucleoproteins to assess evolutionary relationships.

    Sabsay, Kimberly R / Te Velthuis, Aartjan J W

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Negative sense RNA viruses (NSV) include some of the most detrimental human pathogens, including the influenza, Ebola and measles viruses. NSV genomes consist of one or multiple single-stranded RNA molecules that are encapsidated into one or more ... ...

    Abstract Negative sense RNA viruses (NSV) include some of the most detrimental human pathogens, including the influenza, Ebola and measles viruses. NSV genomes consist of one or multiple single-stranded RNA molecules that are encapsidated into one or more ribonucleoprotein (RNP) complexes. Current evolutionary relationships within the NSV phylum are based on alignment of conserved RNA-dependent RNA polymerase (RdRp) domain amino acid sequences. However, the RdRp-based phylogeny does not address whether other core proteins in the NSV genome evolved along the same trajectory. Moreover, the current classification of NSVs does not consistently match the segmented and non-segmented nature of negative-sense virus genomes. Viruses belonging to e.g. the
    Language English
    Publishing date 2024-02-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.16.580771
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Negative and ambisense RNA virus ribonucleocapsids: more than protective armor.

    Sabsay, Kimberly R / Te Velthuis, Aartjan J W

    Microbiology and molecular biology reviews : MMBR

    2023  Volume 87, Issue 4, Page(s) e0008223

    Abstract: SUMMARYNegative and ambisense RNA viruses are the causative agents of important human diseases such as influenza, measles, Lassa fever, and Ebola hemorrhagic fever. The viral genome of these RNA viruses consists of one or more single-stranded RNA ... ...

    Abstract SUMMARYNegative and ambisense RNA viruses are the causative agents of important human diseases such as influenza, measles, Lassa fever, and Ebola hemorrhagic fever. The viral genome of these RNA viruses consists of one or more single-stranded RNA molecules that are encapsidated by viral nucleocapsid proteins to form a ribonucleoprotein complex (RNP). This RNP acts as protection, as a scaffold for RNA folding, and as the context for viral replication and transcription by a viral RNA polymerase. However, the roles of the viral nucleoproteins extend beyond these functions during the viral infection cycle. Recent advances in structural biology techniques and analysis methods have provided new insights into the formation, function, dynamics, and evolution of negative sense virus nucleocapsid proteins, as well as the role that they play in host innate immune responses against viral infection. In this review, we discuss the various roles of nucleocapsid proteins, both in the context of RNPs and in RNA-free states, as well as the open questions that remain.
    MeSH term(s) Humans ; RNA Viruses/genetics ; Ribonucleoproteins/chemistry ; Ribonucleoproteins/genetics ; Ribonucleoproteins/metabolism ; RNA, Viral/chemistry ; Virus Replication/physiology ; Nucleocapsid Proteins/chemistry ; Nucleocapsid Proteins/genetics ; Nucleocapsid Proteins/metabolism ; Virus Diseases
    Chemical Substances Ribonucleoproteins ; RNA, Viral ; Nucleocapsid Proteins
    Language English
    Publishing date 2023-09-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1376131-6
    ISSN 1098-5557 ; 1070-6275 ; 1092-2172
    ISSN (online) 1098-5557 ; 1070-6275
    ISSN 1092-2172
    DOI 10.1128/mmbr.00082-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Decoding the Role of Temperature in RNA Virus Infections.

    Bisht, Karishma / Te Velthuis, Aartjan J W

    mBio

    2022  Volume 13, Issue 5, Page(s) e0202122

    Abstract: RNA viruses include respiratory viruses, such as coronaviruses and influenza viruses, as well as vector-borne viruses, like dengue and West Nile virus. RNA viruses like these encounter various environments when they copy themselves and spread from cell ... ...

    Abstract RNA viruses include respiratory viruses, such as coronaviruses and influenza viruses, as well as vector-borne viruses, like dengue and West Nile virus. RNA viruses like these encounter various environments when they copy themselves and spread from cell to cell or host to host.
    MeSH term(s) Humans ; Temperature ; Virus Replication ; RNA Viruses/genetics ; West Nile virus/genetics ; RNA Virus Infections
    Language English
    Publishing date 2022-08-18
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.02021-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Tinker, tailor, antiviral: RNA virus inhibition by induced recombination.

    Pitre, Emmanuelle / Te Velthuis, Aartjan J W

    Trends in biochemical sciences

    2022  Volume 47, Issue 6, Page(s) 456–458

    Abstract: Nucleotide analogs can help to combat RNA virus growth by stalling the viral RNA polymerase or by introducing lethal mutations into the viral genome. Janissen and Woodman et al. have used single-molecule, sequencing, and virological methods to reveal ... ...

    Abstract Nucleotide analogs can help to combat RNA virus growth by stalling the viral RNA polymerase or by introducing lethal mutations into the viral genome. Janissen and Woodman et al. have used single-molecule, sequencing, and virological methods to reveal that antiviral T-1106 provides a third mechanism of counterattack: inducing recombination.
    MeSH term(s) Antiviral Agents/pharmacology ; Genome, Viral ; RNA Viruses/genetics ; RNA, Viral/genetics ; Recombination, Genetic
    Chemical Substances Antiviral Agents ; RNA, Viral
    Language English
    Publishing date 2022-02-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 194216-5
    ISSN 1362-4326 ; 0968-0004 ; 0376-5067
    ISSN (online) 1362-4326
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2022.01.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Tinker, tailor, antiviral: RNA virus inhibition by induced recombination

    Pitre, Emmanuelle / te Velthuis, Aartjan J.W.

    Trends in biochemical sciences. 2022,

    2022  

    Abstract: Nucleotide analogs can help to combat RNA virus growth by stalling the viral RNA polymerase or by introducing lethal mutations into the viral genome. Janissen and Woodman et al. have used single-molecule, sequencing, and virological methods to reveal ... ...

    Abstract Nucleotide analogs can help to combat RNA virus growth by stalling the viral RNA polymerase or by introducing lethal mutations into the viral genome. Janissen and Woodman et al. have used single-molecule, sequencing, and virological methods to reveal that antiviral T-1106 provides a third mechanism of counterattack: inducing recombination.
    Keywords DNA-directed RNA polymerase ; RNA viruses ; viral genome ; viral growth
    Language English
    Publishing place Elsevier Ltd
    Document type Article
    Note Pre-press version
    ZDB-ID 194220-7
    ISSN 0968-0004 ; 0376-5067
    ISSN 0968-0004 ; 0376-5067
    DOI 10.1016/j.tibs.2022.01.003
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Understanding viral replication and transcription using single-molecule techniques.

    Pitre, Emmanuelle / Te Velthuis, Aartjan J W

    The Enzymes

    2021  Volume 49, Page(s) 83–113

    Abstract: DNA and RNA viruses depend on one or more enzymes to copy and transcribe their genome, such as a polymerase, helicase, or exonuclease. Because of the important role of these enzymes in the virus replication cycle, they are key targets for antiviral ... ...

    Abstract DNA and RNA viruses depend on one or more enzymes to copy and transcribe their genome, such as a polymerase, helicase, or exonuclease. Because of the important role of these enzymes in the virus replication cycle, they are key targets for antiviral development. To better understand the function of these enzymes and their interactions with host and viral factors, biochemical, structural and single-molecule approaches have been used to study them. Each of these techniques has its own strengths, and single-molecule methods have proved particularly powerful in providing insight into the step-sizes of motor proteins, heterogeneity of enzymatic activities, transient conformational changes, and force-sensitivity of reactions. Here we will discuss how single-molecule FRET, magnetic tweezers, optical tweezers, atomic force microscopy and flow stretching approaches have revealed novel insights into polymerase fidelity, the mechanism of action of antivirals, and the protein choreography within replication complexes.
    MeSH term(s) Antiviral Agents ; DNA Helicases ; DNA Viruses/enzymology ; DNA Viruses/physiology ; Optical Tweezers ; RNA Viruses/enzymology ; RNA Viruses/physiology ; Virus Replication
    Chemical Substances Antiviral Agents ; DNA Helicases (EC 3.6.4.-)
    Language English
    Publishing date 2021-09-23
    Publishing country United States
    Document type Journal Article
    ISSN 0423-2607
    ISSN 0423-2607
    DOI 10.1016/bs.enz.2021.07.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Influenza Virus RNA Synthesis and the Innate Immune Response.

    Weis, Sabrina / Te Velthuis, Aartjan J W

    Viruses

    2021  Volume 13, Issue 5

    Abstract: Infection with influenza A and B viruses results in a mild to severe respiratory tract infection. It is widely accepted that many factors affect the severity of influenza disease, including viral replication, host adaptation, innate immune signalling, ... ...

    Abstract Infection with influenza A and B viruses results in a mild to severe respiratory tract infection. It is widely accepted that many factors affect the severity of influenza disease, including viral replication, host adaptation, innate immune signalling, pre-existing immunity, and secondary infections. In this review, we will focus on the interplay between influenza virus RNA synthesis and the detection of influenza virus RNA by our innate immune system. Specifically, we will discuss the generation of various RNA species, host pathogen receptors, and host shut-off. In addition, we will also address outstanding questions that currently limit our knowledge of influenza virus replication and host adaption. Understanding the molecular mechanisms underlying these factors is essential for assessing the pandemic potential of future influenza virus outbreaks.
    MeSH term(s) Animals ; DNA-Directed RNA Polymerases ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Influenza, Human/immunology ; Influenza, Human/virology ; Orthomyxoviridae/genetics ; Orthomyxoviridae/immunology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/virology ; RNA, Viral/biosynthesis ; Receptors, Virus/metabolism ; Viral Proteins ; Virus Replication
    Chemical Substances RNA, Viral ; Receptors, Virus ; Viral Proteins ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
    Language English
    Publishing date 2021-04-28
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13050780
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: The influenza virus RNA polymerase as an innate immune agonist and antagonist.

    Elshina, Elizaveta / Te Velthuis, Aartjan J W

    Cellular and molecular life sciences : CMLS

    2021  Volume 78, Issue 23, Page(s) 7237–7256

    Abstract: Influenza A viruses cause a mild-to-severe respiratory disease that affects millions of people each year. One of the many determinants of disease outcome is the innate immune response to the viral infection. While antiviral responses are essential for ... ...

    Abstract Influenza A viruses cause a mild-to-severe respiratory disease that affects millions of people each year. One of the many determinants of disease outcome is the innate immune response to the viral infection. While antiviral responses are essential for viral clearance, excessive innate immune activation promotes lung damage and disease. The influenza A virus RNA polymerase is one of viral proteins that affect innate immune activation during infection, but the mechanisms behind this activity are not well understood. In this review, we discuss how the viral RNA polymerase can both activate and suppress innate immune responses by either producing immunostimulatory RNA species or directly targeting the components of the innate immune signalling pathway, respectively. Furthermore, we provide a comprehensive overview of the polymerase residues, and their mutations, associated with changes in innate immune activation, and discuss their putative effects on polymerase function based on recent advances in our understanding of the influenza A virus RNA polymerase structure.
    MeSH term(s) Humans ; Immunity, Innate/immunology ; Immunomodulation/immunology ; Influenza A virus/enzymology ; Influenza A virus/genetics ; Influenza A virus/immunology ; Influenza, Human/immunology ; Mitochondria/metabolism ; RNA, Viral/genetics ; RNA-Dependent RNA Polymerase/genetics ; Receptors, Retinoic Acid/metabolism ; Signal Transduction/physiology ; Viral Proteins/genetics ; Virus Replication/genetics
    Chemical Substances PA protein, influenza viruses ; PB2 protein, influenza virus ; PLAAT4 protein, human ; RNA, Viral ; Receptors, Retinoic Acid ; Viral Proteins ; influenza virus polymerase basic protein 1 ; RNA-Dependent RNA Polymerase (EC 2.7.7.48)
    Language English
    Publishing date 2021-10-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-021-03957-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Evolution of transient RNA structure-RNA polymerase interactions in respiratory RNA virus genomes.

    Rigby, Charlotte / Sabsay, Kimberly / Bisht, Karishma / Eggink, Dirk / Jalal, Hamid / Te Velthuis, Aartjan J W

    bioRxiv : the preprint server for biology

    2023  

    Abstract: RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and ... ...

    Abstract RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consists of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.05.25.542331
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase.

    Arcos, Sarah / Han, Alvin X / Te Velthuis, Aartjan J W / Russell, Colin A / Lauring, Adam S

    Virus evolution

    2023  Volume 9, Issue 1, Page(s) vead037

    Abstract: The influenza A virus (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits ... ...

    Abstract The influenza A virus (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (polymerase basic protein 2, polymerase basic protein 1, and polymerase acidic protein). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∼7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To account for uneven sampling of viral sequences over time, we developed a weighted MI (wMI) metric and demonstrate that wMI outperforms raw MI through simulations using a well-sampled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dataset. We then constructed wMI networks of the H3N2 polymerase to extend the inherently pairwise wMI statistic to encompass relationships among larger groups of residues. We included hemagglutinin (HA) in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitch-hiking on antigenic changes in HA. The wMI networks reveal coevolutionary relationships among residues with roles in replication and encapsidation. Inclusion of HA highlighted polymerase-only subgraphs containing residues with roles in the enzymatic functions of the polymerase and host adaptability. This work provides insight into the factors that drive and constrain the rapid evolution of influenza viruses.
    Language English
    Publishing date 2023-05-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/vead037
    Database MEDical Literature Analysis and Retrieval System OnLINE

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