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  1. Article ; Online: Influenza A virus coinfection dynamics are shaped by distinct virus-virus interactions within and between cells.

    Gabrielle K Delima / Ketaki Ganti / Katie E Holmes / Jessica R Shartouny / Anice C Lowen

    PLoS Pathogens, Vol 19, Iss 3, p e

    2023  Volume 1010978

    Abstract: When multiple viral populations propagate within the same host environment, they often shape each other's dynamics. These interactions can be positive or negative and can occur at multiple scales, from coinfection of a cell to co-circulation at a global ... ...

    Abstract When multiple viral populations propagate within the same host environment, they often shape each other's dynamics. These interactions can be positive or negative and can occur at multiple scales, from coinfection of a cell to co-circulation at a global population level. For influenza A viruses (IAVs), the delivery of multiple viral genomes to a cell substantially increases burst size. However, despite its relevance for IAV evolution through reassortment, the implications of this positive density dependence for coinfection between distinct IAVs has not been explored. Furthermore, the extent to which these interactions within the cell shape viral dynamics at the level of the host remains unclear. Here we show that, within cells, diverse coinfecting IAVs strongly augment the replication of a focal strain, irrespective of their homology to the focal strain. Coinfecting viruses with a low intrinsic reliance on multiple infection offer the greatest benefit. Nevertheless, virus-virus interactions at the level of the whole host are antagonistic. This antagonism is recapitulated in cell culture when the coinfecting virus is introduced several hours prior to the focal strain or under conditions conducive to multiple rounds of viral replication. Together, these data suggest that beneficial virus-virus interactions within cells are counterbalanced by competition for susceptible cells during viral propagation through a tissue. The integration of virus-virus interactions across scales is critical in defining the outcomes of viral coinfection.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 612 ; 570
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Beneficial effects of cellular coinfection resolve inefficiency in influenza A virus transcription.

    Jessica R Shartouny / Chung-Young Lee / Gabrielle K Delima / Anice C Lowen

    PLoS Pathogens, Vol 18, Iss 9, p e

    2022  Volume 1010865

    Abstract: For diverse viruses, cellular infection with single vs. multiple virions can yield distinct biological outcomes. We previously found that influenza A/guinea fowl/Hong Kong/WF10/99 (H9N2) virus (GFHK99) displays a particularly high reliance on multiple ... ...

    Abstract For diverse viruses, cellular infection with single vs. multiple virions can yield distinct biological outcomes. We previously found that influenza A/guinea fowl/Hong Kong/WF10/99 (H9N2) virus (GFHK99) displays a particularly high reliance on multiple infection in mammalian cells. Here, we sought to uncover the viral processes underlying this phenotype. We found that the need for multiple infection maps to amino acid 26K of the viral PA protein. PA 26K suppresses endonuclease activity and viral transcription, specifically within cells infected at low multiplicity. In the context of the higher functioning PA 26E, inhibition of PA using baloxavir acid augments reliance on multiple infection. Together, these data suggest a model in which sub-optimal activity of the GFHK99 endonuclease results in inefficient priming of viral transcription, an insufficiency which can be overcome with the introduction of additional viral ribonucleoprotein templates to the cell. More broadly, the finding that deficiency in a core viral function is ameliorated through multiple infection suggests that the fitness effects of many viral mutations are likely to be modulated by multiplicity of infection, such that the shape of fitness landscapes varies with viral densities.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Timing of exposure is critical in a highly sensitive model of SARS-CoV-2 transmission.

    Ketaki Ganti / Lucas M Ferreri / Chung-Young Lee / Camden R Bair / Gabrielle K Delima / Kate E Holmes / Mehul S Suthar / Anice C Lowen

    PLoS Pathogens, Vol 18, Iss 3, p e

    2022  Volume 1010181

    Abstract: Transmission efficiency is a critical factor determining the size of an outbreak of infectious disease. Indeed, the propensity of SARS-CoV-2 to transmit among humans precipitated and continues to sustain the COVID-19 pandemic. Nevertheless, the number of ...

    Abstract Transmission efficiency is a critical factor determining the size of an outbreak of infectious disease. Indeed, the propensity of SARS-CoV-2 to transmit among humans precipitated and continues to sustain the COVID-19 pandemic. Nevertheless, the number of new cases among contacts is highly variable and underlying reasons for wide-ranging transmission outcomes remain unclear. Here, we evaluated viral spread in golden Syrian hamsters to define the impact of temporal and environmental conditions on the efficiency of SARS-CoV-2 transmission through the air. Our data show that exposure periods as brief as one hour are sufficient to support robust transmission. However, the timing after infection is critical for transmission success, with the highest frequency of transmission to contacts occurring at times of peak viral load in the donor animals. Relative humidity and temperature had no detectable impact on transmission when exposures were carried out with optimal timing and high inoculation dose. However, contrary to expectation, trends observed with sub-optimal exposure timing and lower inoculation dose suggest improved transmission at high relative humidity or high temperature. In sum, among the conditions tested, our data reveal the timing of exposure to be the strongest determinant of SARS-CoV-2 transmission success and implicate viral load as an important driver of transmission.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 535
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Dysregulation of M segment gene expression contributes to influenza A virus host restriction.

    Brenda M Calderon / Shamika Danzy / Gabrielle K Delima / Nathan T Jacobs / Ketaki Ganti / Megan R Hockman / Graeme L Conn / Anice C Lowen / John Steel

    PLoS Pathogens, Vol 15, Iss 8, p e

    2019  Volume 1007892

    Abstract: The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate the genetic contributions of the M segment to host adaptation, and the underlying mechanisms, we examined a panel of ... ...

    Abstract The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate the genetic contributions of the M segment to host adaptation, and the underlying mechanisms, we examined a panel of isogenic viruses that carry avian- or human-derived M segments. Avian, but not human, M segments restricted viral growth and transmission in mammalian model systems, and the restricted growth correlated with increased expression of M2 relative to M1. M2 overexpression was associated with intracellular accumulation of autophagosomes, which was alleviated by interference of the viral proton channel activity by amantadine treatment. As M1 and M2 are expressed from the M mRNA through alternative splicing, we separated synonymous and non-synonymous changes that differentiate human and avian M segments and found that dysregulation of gene expression leading to M2 overexpression diminished replication, irrespective of amino acid composition of M1 or M2. Moreover, in spite of efficient replication, virus possessing a human M segment that expressed avian M2 protein at low level did not transmit efficiently. We conclude that (i) determinants of transmission reside in the IAV M2 protein, and that (ii) control of M segment gene expression is a critical aspect of IAV host adaptation needed to prevent M2-mediated dysregulation of vesicular homeostasis.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2019-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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