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  1. Article: Counterintuitive effect of antiviral therapy on influenza A-SARS-CoV-2 coinfection due to viral interference.

    Cheemarla, Nagarjuna R / Mihaylova, Valia T / Watkins, Timothy A / Foxman, Ellen F

    bioRxiv : the preprint server for biology

    2023  

    Abstract: The resurgence of influenza and continued circulation of SARS-CoV-2 raise the question of how these viruses interact in a co-exposed host. Here we studied virus-virus and host-virus interactions during influenza A virus (IAV) -SARS-CoV-2 coinfection ... ...

    Abstract The resurgence of influenza and continued circulation of SARS-CoV-2 raise the question of how these viruses interact in a co-exposed host. Here we studied virus-virus and host-virus interactions during influenza A virus (IAV) -SARS-CoV-2 coinfection using differentiated cultures of the human airway epithelium. Coexposure to IAV enhanced the tissue antiviral response during SARS-CoV-2 infection and suppressed SARS-CoV-2 replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the antiviral response and paradoxically restored SARS-CoV-2 replication. These results highlight the importance of diagnosing coinfections and compel further study of how coinfections impact the outcome of antiviral therapy.
    Language English
    Publishing date 2023-02-08
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.07.527372
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Viral interference during influenza A-SARS-CoV-2 coinfection of the human airway epithelium and reversal by oseltamivir.

    Cheemarla, Nagarjuna R / Watkins, Timothy A / Mihaylova, Valia T / Foxman, Ellen F

    The Journal of infectious diseases

    2023  

    Abstract: To gain insight into interactions among respiratory viruses, we modeled influenza A virus (IAV) - SARS-CoV-2 coinfections using differentiated human airway epithelial cultures. Replicating IAV induced a more robust interferon response than SARS-CoV-2 and ...

    Abstract To gain insight into interactions among respiratory viruses, we modeled influenza A virus (IAV) - SARS-CoV-2 coinfections using differentiated human airway epithelial cultures. Replicating IAV induced a more robust interferon response than SARS-CoV-2 and suppressed SARS-CoV-2 replication in both sequential and simultaneous infections, whereas SARS-CoV-2 did not enhance host cell defense during influenza infection or suppress IAV replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the host antiviral response and restored SARS-CoV-2 replication. These results demonstrate how perturbations in one viral infection can impact its effect on a coinfecting virus.
    Language English
    Publishing date 2023-09-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiad402
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Counterintuitive effect of antiviral therapy on influenza A-SARS-CoV-2 coinfection due to viral interference

    Cheemarla, Nagarjuna R. / Mihaylova, Valia T. / Watkins, Timothy A. / Foxman, Ellen F.

    bioRxiv

    Abstract: The resurgence of influenza and continued circulation of SARS-CoV-2 raise the question of how these viruses interact in a co-exposed host. Here we studied virus-virus and host-virus interactions during influenza A virus (IAV) -SARS-CoV-2 coinfection ... ...

    Abstract The resurgence of influenza and continued circulation of SARS-CoV-2 raise the question of how these viruses interact in a co-exposed host. Here we studied virus-virus and host-virus interactions during influenza A virus (IAV) -SARS-CoV-2 coinfection using differentiated cultures of the human airway epithelium. Coexposure to IAV enhanced the tissue antiviral response during SARS-CoV-2 infection and suppressed SARS-CoV-2 replication. Oseltamivir, an antiviral targeting influenza, reduced IAV replication during coinfection but also reduced the antiviral response and paradoxically restored SARS-CoV-2 replication. These results highlight the importance of diagnosing coinfections and compel further study of how coinfections impact the outcome of antiviral therapy.
    Keywords covid19
    Language English
    Publishing date 2023-02-08
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.02.07.527372
    Database COVID19

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  4. Article ; Online: Taxane chemotherapy induces stromal injury that leads to breast cancer dormancy escape.

    Ganesan, Ramya / Bhasin, Swati S / Bakhtiary, Mojtaba / Krishnan, Upaasana / Cheemarla, Nagarjuna R / Thomas, Beena E / Bhasin, Manoj K / Sukhatme, Vikas P

    PLoS biology

    2023  Volume 21, Issue 9, Page(s) e3002275

    Abstract: A major cause of cancer recurrence following chemotherapy is cancer dormancy escape. Taxane-based chemotherapy is standard of care in breast cancer treatment aimed at killing proliferating cancer cells. Here, we demonstrate that docetaxel injures stromal ...

    Abstract A major cause of cancer recurrence following chemotherapy is cancer dormancy escape. Taxane-based chemotherapy is standard of care in breast cancer treatment aimed at killing proliferating cancer cells. Here, we demonstrate that docetaxel injures stromal cells, which release protumor cytokines, IL-6 and granulocyte colony stimulating factor (G-CSF), that in turn invoke dormant cancer outgrowth both in vitro and in vivo. Single-cell transcriptomics shows a reprogramming of awakened cancer cells including several survival cues such as stemness, chemoresistance in a tumor stromal organoid (TSO) model, as well as an altered tumor microenvironment (TME) with augmented protumor immune signaling in a syngeneic mouse breast cancer model. IL-6 plays a role in cancer cell proliferation, whereas G-CSF mediates tumor immunosuppression. Pathways and differential expression analyses confirmed MEK as the key regulatory molecule in cancer cell outgrowth and survival. Antibody targeting of protumor cytokines (IL-6, G-CSF) or inhibition of cytokine signaling via MEK/ERK pathway using selumetinib prior to docetaxel treatment prevented cancer dormancy outgrowth suggesting a novel therapeutic strategy to prevent cancer recurrence.
    MeSH term(s) Animals ; Mice ; Docetaxel/pharmacology ; Interleukin-6 ; Taxoids/pharmacology ; Taxoids/therapeutic use ; Cytokines ; Granulocyte Colony-Stimulating Factor ; Mitogen-Activated Protein Kinase Kinases ; Neoplasms
    Chemical Substances Docetaxel (15H5577CQD) ; Interleukin-6 ; taxane (1605-68-1) ; Taxoids ; Cytokines ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Mitogen-Activated Protein Kinase Kinases (EC 2.7.12.2)
    Language English
    Publishing date 2023-09-12
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2126776-5
    ISSN 1545-7885 ; 1544-9173
    ISSN (online) 1545-7885
    ISSN 1544-9173
    DOI 10.1371/journal.pbio.3002275
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: How does the human metapneumovirus regulate neutrophil infiltration into the airways?

    Cheemarla, Nagarjuna R / Guerrero-Plata, Antonieta

    Future virology

    2018  Volume 13, Issue 4, Page(s) 233–235

    Language English
    Publishing date 2018-02-21
    Publishing country England
    Document type Journal Article
    ISSN 1746-0794
    ISSN 1746-0794
    DOI 10.2217/fvl-2018-0001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Human Metapneumovirus Induces Mucin 19 Which Contributes to Viral Pathogenesis.

    McBride, Kaitlin / Banos-Lara, Ma Del Rocio / Cheemarla, Nagarjuna R / Guerrero-Plata, Antonieta

    Pathogens (Basel, Switzerland)

    2020  Volume 9, Issue 9

    Abstract: Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms ... ...

    Abstract Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms to severe bronchiolitis and pneumonia. The production of mucus is a common feature during HMPV infection, but its contribution to HMPV-induced pathogenesis and immune response is largely unknown. Mucins are a major component of mucus and they could have an impact on how the host responds to infections. Using an in vitro system and a mouse model of infection, we identified that Mucin 19 is predominantly expressed in the respiratory tract upon HMPV infection. Moreover, the lack of Muc19 led to an improved disease, lower lung viral titers and a decrease in the number of CD4+ T cells. These data indicate that mucin 19 contributes to the activation of the immune response to HMPV and to HMPV-induced pathogenesis.
    Language English
    Publishing date 2020-09-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens9090726
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Human Metapneumovirus Attachment Protein Contributes to Neutrophil Recruitment into the Airways of Infected Mice.

    Cheemarla, Nagarjuna R / Guerrero-Plata, Antonieta

    Viruses

    2017  Volume 9, Issue 10

    Abstract: Human Metapneumovirus (HMPV) is a leading respiratory pathogen that causes lower respiratory tract infections worldwide. Acute HMPV infection induces an exacerbated inflammatory neutrophilic response leading to bronchiolitis and pneumonia. However, the ... ...

    Abstract Human Metapneumovirus (HMPV) is a leading respiratory pathogen that causes lower respiratory tract infections worldwide. Acute HMPV infection induces an exacerbated inflammatory neutrophilic response leading to bronchiolitis and pneumonia. However, the mechanism by which the virus regulates neutrophil infiltration into the airways still remains unexplored. In this work, we used an experimental mouse model of HMPV infection to demonstrate that the attachment (G) protein of HMPV contributes to the recruitment of neutrophils into the airways and modulate the production of neutrophil chemoattractants and Type I IFN responses, specifically IFN-α. These findings provide the first evidence that the HMPV G protein contributes to the in vivo neutrophilic response to HMPV infection and furthers our understanding on virus induced inflammatory responses in the airways.
    Language English
    Publishing date 2017-10-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v9100310
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  8. Article: Magnitude and timing of the antiviral response determine SARS-CoV-2 replication early in infection.

    Cheemarla, Nagarjuna R / Watkins, Timothy A / Mihaylova, Valia T / Wang, Bao / Zhao, Dejian / Wang, Guilin / Landry, Marie L / Foxman, Ellen F

    medRxiv : the preprint server for health sciences

    2021  

    Abstract: The interferon response is a potent antiviral defense mechanism, but its effectiveness depends on its timing relative to viral replication. Here, we report viral replication and host response kinetics in patients at the start of SARS-CoV-2 infection and ... ...

    Abstract The interferon response is a potent antiviral defense mechanism, but its effectiveness depends on its timing relative to viral replication. Here, we report viral replication and host response kinetics in patients at the start of SARS-CoV-2 infection and explore the impact of these kinetics experimentally. In both longitudinal patient nasopharyngeal samples and airway epithelial organoids, we found that SARS-CoV-2 initially replicated exponentially with a doubling time of ~6hr, and induced interferon stimulated genes (ISGs) with delayed timing relative to viral replication. Prior exposure to rhinovirus increased ISG levels and blocked SARS-CoV-2 replication. Conversely, inhibiting ISG induction abrogated interference by rhinovirus and enhanced SARS-CoV-2 replication rate. These results demonstrate the importance of initial interferon-mediated defenses in determining the extent to which SARS-CoV-2 can replicate at the start of infection and indicate that biological variables that alter the airway interferon response, including heterologous induction of innate immunity by other viruses, could profoundly impact SARS-CoV-2 susceptibility and transmission.
    Language English
    Publishing date 2021-01-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.01.22.21249812
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Human Metapneumovirus Induces Mucin 19 Which Contributes to Viral Pathogenesis

    Kaitlin McBride / Ma. del Rocio Banos-Lara / Nagarjuna R. Cheemarla / Antonieta Guerrero-Plata

    Pathogens, Vol 9, Iss 726, p

    2020  Volume 726

    Abstract: Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms ... ...

    Abstract Human Metapneumovirus (HMPV) remains one of the most common viral infections causing acute respiratory tract infections, especially in young children, elderly, and immunocompromised populations. Clinical symptoms can range from mild respiratory symptoms to severe bronchiolitis and pneumonia. The production of mucus is a common feature during HMPV infection, but its contribution to HMPV-induced pathogenesis and immune response is largely unknown. Mucins are a major component of mucus and they could have an impact on how the host responds to infections. Using an in vitro system and a mouse model of infection, we identified that Mucin 19 is predominantly expressed in the respiratory tract upon HMPV infection. Moreover, the lack of Muc19 led to an improved disease, lower lung viral titers and a decrease in the number of CD4+ T cells. These data indicate that mucin 19 contributes to the activation of the immune response to HMPV and to HMPV-induced pathogenesis.
    Keywords HMPV ; Muc19 ; mucins ; immune response ; human metapneumovirus ; respiratory tract ; Medicine ; R
    Subject code 572
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Dynamic innate immune response determines susceptibility to SARS-CoV-2 infection and early replication kinetics.

    Cheemarla, Nagarjuna R / Watkins, Timothy A / Mihaylova, Valia T / Wang, Bao / Zhao, Dejian / Wang, Guilin / Landry, Marie L / Foxman, Ellen F

    The Journal of experimental medicine

    2021  Volume 218, Issue 8

    Abstract: Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and the replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting ... ...

    Abstract Initial replication of SARS-CoV-2 in the upper respiratory tract is required to establish infection, and the replication level correlates with the likelihood of viral transmission. Here, we examined the role of host innate immune defenses in restricting early SARS-CoV-2 infection using transcriptomics and biomarker-based tracking in serial patient nasopharyngeal samples and experiments with airway epithelial organoids. SARS-CoV-2 initially replicated exponentially, with a doubling time of ∼6 h, and induced interferon-stimulated genes (ISGs) in the upper respiratory tract, which rose with viral replication and peaked just as viral load began to decline. Rhinovirus infection before SARS-CoV-2 exposure accelerated ISG responses and prevented SARS-CoV-2 replication. Conversely, blocking ISG induction during SARS-CoV-2 infection enhanced viral replication from a low infectious dose. These results show that the activity of ISG-mediated defenses at the time of SARS-CoV-2 exposure impacts infection progression and that the heterologous antiviral response induced by a different virus can protect against SARS-CoV-2.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/immunology ; COVID-19/virology ; Case-Control Studies ; Chemokine CXCL10/metabolism ; Disease Susceptibility/immunology ; Female ; Gene Expression Profiling ; Host-Pathogen Interactions/physiology ; Humans ; Immunity, Innate/physiology ; Interferons/genetics ; Interferons/immunology ; Interferons/metabolism ; Male ; Middle Aged ; Nasopharynx/virology ; Picornaviridae Infections/immunology ; Picornaviridae Infections/virology ; SARS-CoV-2/genetics ; SARS-CoV-2/physiology ; Viral Load ; Virus Replication
    Chemical Substances CXCL10 protein, human ; Chemokine CXCL10 ; Interferons (9008-11-1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Language English
    Publishing date 2021-06-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20210583
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