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  1. Article ; Online: Within-Host Viral Diversity: A Window into Viral Evolution.

    Lauring, Adam S

    Annual review of virology

    2020  Volume 7, Issue 1, Page(s) 63–81

    Abstract: The evolutionary dynamics of a virus can differ within hosts and across populations. Studies of within-host evolution provide an important link between experimental studies of virus evolution and large-scale phylodynamic analyses. They can determine the ... ...

    Abstract The evolutionary dynamics of a virus can differ within hosts and across populations. Studies of within-host evolution provide an important link between experimental studies of virus evolution and large-scale phylodynamic analyses. They can determine the extent to which global processes are recapitulated on local scales and how accurately experimental infections model natural ones. They may also inform epidemiologic models of disease spread and reveal how host-level dynamics contribute to a virus's evolution at a larger scale. Over the last decade, advances in viral sequencing have enabled detailed studies of viral genetic diversity within hosts. I review how within-host diversity is sampled, measured, and expressed, and how comparative studies of viral diversity can be leveraged to elucidate a virus's evolutionary dynamics. These concepts are illustrated with detailed reviews of recent research on the within-host evolution of influenza virus, dengue virus, and cytomegalovirus.
    MeSH term(s) Cytomegalovirus/genetics ; Dengue Virus/genetics ; Evolution, Molecular ; Genetic Variation ; Host-Pathogen Interactions ; Humans ; Influenza A virus/genetics ; Viruses/genetics
    Language English
    Publishing date 2020-06-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2764224-0
    ISSN 2327-0578 ; 2327-056X
    ISSN (online) 2327-0578
    ISSN 2327-056X
    DOI 10.1146/annurev-virology-010320-061642
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Variants of SARS-CoV-2.

    Lauring, Adam S / Malani, Preeti N

    JAMA

    2021  

    Language English
    Publishing date 2021-08-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.2021.14181
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  3. Article ; Online: Genetic Variants of SARS-CoV-2-What Do They Mean?

    Lauring, Adam S / Hodcroft, Emma B

    JAMA

    2021  Volume 325, Issue 6, Page(s) 529–531

    MeSH term(s) Animals ; COVID-19/veterinary ; COVID-19/virology ; COVID-19 Vaccines/immunology ; Genetic Variation ; Humans ; Mink ; Mutation ; Phylogeny ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-01-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2958-0
    ISSN 1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
    ISSN (online) 1538-3598
    ISSN 0254-9077 ; 0002-9955 ; 0098-7484
    DOI 10.1001/jama.2020.27124
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  4. Article ; Online: Incidence and outcomes of hospital-associated respiratory virus infections by viral species.

    Petrie, Joshua G / Moore, Riley / Lauring, Adam S / Kaye, Keith S

    Infection control and hospital epidemiology

    2023  Volume 45, Issue 5, Page(s) 618–629

    Abstract: Background: Although the incidence of hospital-associated respiratory virus infection (HARVI) is well recognized, the risk factors for infection and impact on patient outcomes are not well characterized.: Methods: We identified a cohort of all ... ...

    Abstract Background: Although the incidence of hospital-associated respiratory virus infection (HARVI) is well recognized, the risk factors for infection and impact on patient outcomes are not well characterized.
    Methods: We identified a cohort of all inpatient admissions ≥24 hours duration at a single academic medical center from 2017 to 2020. HARVI were defined as respiratory virus detected in a test ordered after the 95th percentile of the virus-specific incubation period. Risk factors for HARVI were assessed using Cox proportional hazards models of the competing outcomes of HARVI and discharge. The associations between time-varying HARVI status and the rates of ICU admission, discharge, and in-hospital death were estimated using Cox-proportional hazards models in a competing risk framework.
    Results: HARVI incidences were 8.8 and 3.0 per 10,000 admission days for pediatric and adult patients, respectively. For adults, congestive heart failure, renal disease, and cancer increased HARVI risk independent of their associations with length of stay. HARVI risk was also elevated for patients admitted in September-June relative to July admissions. For pediatric patients, cardiovascular and respiratory conditions, cancer, medical device dependence, and admission in December increased HARVI risk. Lengths of stay were longer for adults with HARVI compared to those without, and hospital-associated influenza A was associated with increased risk of death. Rates of ICU admission were increased in the 5 days after HARVI identification for adult and pediatric patients. HARVI was not associated with length of stay or death among pediatric patients.
    Conclusions: HARVI is associated chronic health conditions and increases morbidity and mortality.
    MeSH term(s) Adult ; Humans ; Child ; Incidence ; Hospital Mortality ; Hospitals ; Virus Diseases ; Neoplasms ; Length of Stay ; Retrospective Studies ; Intensive Care Units
    Language English
    Publishing date 2023-12-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639378-0
    ISSN 1559-6834 ; 0195-9417 ; 0899-823X
    ISSN (online) 1559-6834
    ISSN 0195-9417 ; 0899-823X
    DOI 10.1017/ice.2023.263
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  5. Article ; Online: Lessons from Reverse Translation.

    Lauring, Adam S

    PLoS pathogens

    2016  Volume 12, Issue 6, Page(s) e1005516

    Language English
    Publishing date 2016-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1005516
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  6. Article ; Online: SARS-CoV-2 Vaccine Strain Selection: Guidance From Influenza.

    Monto, Arnold S / Lauring, Adam S / Martin, Emily T

    The Journal of infectious diseases

    2022  Volume 227, Issue 1, Page(s) 4–8

    Abstract: When first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming ... ...

    Abstract When first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) COVID-19 vaccines. It is hoped that, if COVID-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary. Recommendations on whom should receive the booster would be based on conditions at that time.
    MeSH term(s) Humans ; Influenza Vaccines ; Influenza, Human/prevention & control ; COVID-19 Vaccines ; COVID-19/prevention & control ; SARS-CoV-2
    Chemical Substances Influenza Vaccines ; COVID-19 Vaccines
    Language English
    Publishing date 2022-11-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac454
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  7. 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
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  8. 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

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The influenza A (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 ... ...

    Abstract The influenza A (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 (PB2, PB1, and PA). 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 metric (wMI) and demonstrate that wMI outperforms raw MI through simulations using a well-sampled 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 HA in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitchhiking 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 2023-02-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.16.528850
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  9. Article ; Online: Deep mutational scanning reveals the functional constraints and evolutionary potential of the influenza A virus PB1 protein.

    Li, Yuan / Arcos, Sarah / Sabsay, Kimberly R / Te Velthuis, Aartjan J W / Lauring, Adam S

    Journal of virology

    2023  Volume 97, Issue 11, Page(s) e0132923

    Abstract: Importance: The influenza virus polymerase is important for adaptation to new hosts and, as a determinant of mutation rate, for the process of adaptation itself. We performed a deep mutational scan of the polymerase basic 1 (PB1) protein to gain ... ...

    Abstract Importance: The influenza virus polymerase is important for adaptation to new hosts and, as a determinant of mutation rate, for the process of adaptation itself. We performed a deep mutational scan of the polymerase basic 1 (PB1) protein to gain insights into the structural and functional constraints on the influenza RNA-dependent RNA polymerase. We find that PB1 is highly constrained at specific sites that are only moderately predicted by the global structure or larger domain. We identified a number of beneficial mutations, many of which have been shown to be functionally important or observed in influenza virus' natural evolution. Overall, our atlas of PB1 mutations and their fitness impacts serves as an important resource for future studies of influenza replication and evolution.
    MeSH term(s) Influenza A virus/genetics ; Influenza A virus/metabolism ; Mutation/genetics ; Viral Proteins/chemistry ; Viral Proteins/genetics ; Viral Proteins/metabolism ; Virus Replication/genetics ; RNA-Dependent RNA Polymerase/chemistry ; RNA-Dependent RNA Polymerase/genetics ; RNA-Dependent RNA Polymerase/metabolism ; Evolution, Molecular ; Orthomyxoviridae Infections/virology
    Chemical Substances Viral Proteins ; influenza virus polymerase basic protein 1 ; RNA-Dependent RNA Polymerase (EC 2.7.7.48)
    Language English
    Publishing date 2023-10-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.01329-23
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  10. Article ; Online: Influenza A(H7N9) Virus Evolution: Which Genetic Mutations Are Antigenically Important?

    Petrie, Joshua G / Lauring, Adam S

    The Journal of infectious diseases

    2018  Volume 219, Issue 1, Page(s) 3–5

    MeSH term(s) Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Hemagglutinins ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; Mutation
    Chemical Substances Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins
    Language English
    Publishing date 2018-07-03
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiy409
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