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  1. Article ; Online: Herpes simplex virus-1 utilizes the host actin cytoskeleton for its release from axonal growth cones.

    Danastas, Kevin / Larsen, Ava / Jobson, Sophie / Guo, Gerry / Cunningham, Anthony L / Miranda-Saksena, Monica

    PLoS pathogens

    2022  Volume 18, Issue 1, Page(s) e1010264

    Abstract: Herpes simplex virus type 1 (HSV-1) has evolved mechanisms to exploit the host cytoskeleton during entry, replication and exit from cells. In this study, we determined the role of actin and the molecular motor proteins, myosin II and myosin V, in the ... ...

    Abstract Herpes simplex virus type 1 (HSV-1) has evolved mechanisms to exploit the host cytoskeleton during entry, replication and exit from cells. In this study, we determined the role of actin and the molecular motor proteins, myosin II and myosin V, in the transport and release of HSV-1 from axon termini, or growth cones. Using compartmentalized neuronal devices, we showed that inhibition of actin polymerization, but not actin branching, significantly reduced the release of HSV-1 from axons. Furthermore, we showed that inhibition of myosin V, but not myosin II, also significantly reduced the release of HSV-1 from axons. Using confocal and electron microscopy, we determined that viral components are transported along axons to growth cones, despite actin or myosin inhibition. Overall, our study supports the role of actin in virus release from axonal growth cones and suggests myosin V as a likely candidate involved in this process.
    MeSH term(s) Actin Cytoskeleton/virology ; Animals ; Axonal Transport/physiology ; Growth Cones/ultrastructure ; Growth Cones/virology ; Herpes Simplex/virology ; Herpesvirus 1, Human ; Rats ; Rats, Wistar ; Virus Release/physiology
    Language English
    Publishing date 2022-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010264
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Interferon inhibits the release of herpes simplex virus-1 from the axons of sensory neurons.

    Danastas, Kevin / Guo, Gerry / Merjane, Jessica / Hong, Nathan / Larsen, Ava / Miranda-Saksena, Monica / Cunningham, Anthony L

    mBio

    2023  Volume 14, Issue 5, Page(s) e0181823

    Abstract: Importance: Herpes simplex virus-1 (HSV-1) is a human pathogen known to cause cold sores and genital herpes. HSV-1 establishes lifelong infections in our sensory neurons, with no cure or vaccine available. HSV-1 can reactivate sporadically and travel ... ...

    Abstract Importance: Herpes simplex virus-1 (HSV-1) is a human pathogen known to cause cold sores and genital herpes. HSV-1 establishes lifelong infections in our sensory neurons, with no cure or vaccine available. HSV-1 can reactivate sporadically and travel back along sensory nerves, where it can form lesions in the oral and genital mucosa, eye, and skin, or be shed asymptomatically. New treatment options are needed as resistance is emerging to current antiviral therapies. Here, we show that interferons (IFNs) are capable of blocking virus release from nerve endings, potentially stopping HSV-1 transmission into the skin. Furthermore, we show that IFNγ has the potential to have widespread antiviral effects in the neuron and may have additional effects on HSV-1 reactivation. Together, this study identifies new targets for the development of immunotherapies to stop the spread of HSV-1 from the nerves into the skin.
    MeSH term(s) Humans ; Herpesvirus 1, Human/physiology ; Interferons ; Sensory Receptor Cells/pathology ; Axons/pathology ; Antiviral Agents ; Herpes Simplex
    Chemical Substances Interferons (9008-11-1) ; Antiviral Agents
    Language English
    Publishing date 2023-09-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.01818-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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