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  1. Article ; Online: Herpes Simplex Virus Type 1 Interactions with the Interferon System.

    Danastas, Kevin / Miranda-Saksena, Monica / Cunningham, Anthony L

    International journal of molecular sciences

    2020  Volume 21, Issue 14

    Abstract: The interferon (IFN) system is one of the first lines of defense activated against invading viral pathogens. Upon secretion, IFNs activate a signaling cascade resulting in the production of several interferon stimulated genes (ISGs), which work to limit ... ...

    Abstract The interferon (IFN) system is one of the first lines of defense activated against invading viral pathogens. Upon secretion, IFNs activate a signaling cascade resulting in the production of several interferon stimulated genes (ISGs), which work to limit viral replication and establish an overall anti-viral state. Herpes simplex virus type 1 is a ubiquitous human pathogen that has evolved to downregulate the IFN response and establish lifelong latent infection in sensory neurons of the host. This review will focus on the mechanisms by which the host innate immune system detects invading HSV-1 virions, the subsequent IFN response generated to limit viral infection, and the evasion strategies developed by HSV-1 to evade the immune system and establish latency in the host.
    MeSH term(s) Animals ; Herpes Simplex/immunology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/metabolism ; Herpesvirus 1, Human/pathogenicity ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Interferons/metabolism ; Signal Transduction/genetics ; Signal Transduction/immunology ; Toll-Like Receptors/immunology ; Virus Replication/genetics
    Chemical Substances Toll-Like Receptors ; Interferons (9008-11-1)
    Language English
    Publishing date 2020-07-21
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21145150
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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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  3. 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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  4. Article ; Online: The Use of Microfluidic Neuronal Devices to Study the Anterograde Axonal Transport of Herpes Simplex Virus-1.

    Danastas, Kevin / Cunningham, Anthony L / Miranda-Saksena, Monica

    Methods in molecular biology (Clifton, N.J.)

    2019  Volume 2060, Page(s) 409–418

    Abstract: Understanding how herpes simplex virus-1 (HSV-1) interacts with different parts of the neuron is fundamental in understanding the mechanisms behind HSV-1 transport during primary and recurrent infections. In this chapter, we describe a unique neuronal ... ...

    Abstract Understanding how herpes simplex virus-1 (HSV-1) interacts with different parts of the neuron is fundamental in understanding the mechanisms behind HSV-1 transport during primary and recurrent infections. In this chapter, we describe a unique neuronal culture system that is capable of compartmentalizing neuronal cell bodies from their axons to study the transport of HSV-1 along axons. The ability to separate neuronal cell bodies and axons provides a unique model to investigate the mechanisms used by HSV-1 for viral transport, assembly, and exit from different parts of the neuron.
    MeSH term(s) Animals ; Axonal Transport ; Axons/metabolism ; Axons/pathology ; Axons/virology ; Ganglia, Spinal/metabolism ; Ganglia, Spinal/pathology ; Ganglia, Spinal/virology ; Herpesvirus 1, Human/metabolism ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques ; Rats ; Rats, Wistar
    Language English
    Publishing date 2019-10-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-9814-2_25
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Ovarian Hyperstimulation Reduces Vascular Endothelial Growth Factor-A During Uterine Receptivity.

    Danastas, Kevin / Whittington, Camilla M / Dowland, Samson N / Combes, Valery / Murphy, Christopher R / Lindsay, Laura A

    Reproductive sciences (Thousand Oaks, Calif.)

    2018  Volume 26, Issue 2, Page(s) 259–268

    Abstract: The angiogenic factor vascular endothelial growth factor-A (VEGFA) plays a critical role during early pregnancy in many species including the rat, and any alterations in VEGFA levels can severely impact blastocyst implantation rates. The rat ovarian ... ...

    Abstract The angiogenic factor vascular endothelial growth factor-A (VEGFA) plays a critical role during early pregnancy in many species including the rat, and any alterations in VEGFA levels can severely impact blastocyst implantation rates. The rat ovarian hyperstimulation (OH) model is useful in studying how the induction of superovulation affects VEGFA levels and endometrial receptivity to blastocyst implantation. The present study shows that the major isoform in the rat uterus, Vegf
    MeSH term(s) Animals ; Estradiol/pharmacology ; Female ; Ovarian Hyperstimulation Syndrome/metabolism ; Ovulation Induction ; Progesterone/pharmacology ; Rats ; Rats, Wistar ; Uterus/drug effects ; Uterus/metabolism ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism
    Chemical Substances Vascular Endothelial Growth Factor A ; Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2018-04-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2276411-2
    ISSN 1933-7205 ; 1933-7191
    ISSN (online) 1933-7205
    ISSN 1933-7191
    DOI 10.1177/1933719118768703
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4113: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article: Expression of vascular endothelial growth factor A isoforms is dysregulated in women with endometriosis.

    Danastas, Kevin / Miller, Emily J / Hey-Cunningham, Alison J / Murphy, Christopher R / Lindsay, Laura A

    Reproduction, fertility, and development

    2017  Volume 30, Issue 4, Page(s) 651–657

    Abstract: Angiogenesis is a critical step in the development of ectopic lesions during endometriosis. Although total vascular endothelial growth factor (VEGF) A is elevated in the peritoneal fluid of women with endometriosis, there are contradictory reports on how ...

    Abstract Angiogenesis is a critical step in the development of ectopic lesions during endometriosis. Although total vascular endothelial growth factor (VEGF) A is elevated in the peritoneal fluid of women with endometriosis, there are contradictory reports on how levels of total endometrial VEGFA are altered in this disease. Furthermore, limited research is available on different VEGFA isoforms in women with endometriosis. Thus, the aim of the present study was to analyse levels of various VEGFA isoforms in women with and without endometriosis at different stages of the menstrual cycle. Quantitative polymerase chain reaction analysis showed that total VEGFA was highest during menstruation in endometriosis compared with controls (P=0.0373). VEGF121 and VEGF189 were similarly highest during menstruation in endometriosis compared with controls (P=0.0165 and 0.0154 respectively). The present study is also the first to identify the natural expression of VEGF111 in human tissue, which is also highest during menstruation in endometriosis (P=0.0464). This discovery of the natural production of VEGF111 in human endometrium, as well as the upregulation of VEGFA isoforms during menstruation in endometriosis, may shed further light on the development and progression of the disease, and improve our understanding of the regulation of endometrial angiogenesis.
    MeSH term(s) Adolescent ; Adult ; Endometriosis/genetics ; Endometriosis/metabolism ; Endometrium/metabolism ; Female ; Gene Expression Regulation ; Humans ; Menstrual Cycle/genetics ; Menstrual Cycle/metabolism ; Menstruation/genetics ; Menstruation/metabolism ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Vascular Endothelial Growth Factor A/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Young Adult
    Chemical Substances Protein Isoforms ; Vascular Endothelial Growth Factor A
    Language English
    Publishing date 2017-10-10
    Publishing country Australia
    Document type Journal Article
    ZDB-ID 1019913-5
    ISSN 1448-5990 ; 1031-3613
    ISSN (online) 1448-5990
    ISSN 1031-3613
    DOI 10.1071/RD17184
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2756: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Expression of VEGF

    Whittington, Camilla M / Danastas, Kevin / Grau, Georges E / Murphy, Christopher R / Thompson, Michael B

    Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology

    2017  Volume 187, Issue 2, Page(s) 353–360

    Abstract: Vascular endothelial growth factor A is a major mediator of angiogenesis, a critically important process in vertebrate growth and development as well as pregnancy. Here we report for the first time the expression of a rare and unusually potent splice ... ...

    Abstract Vascular endothelial growth factor A is a major mediator of angiogenesis, a critically important process in vertebrate growth and development as well as pregnancy. Here we report for the first time the expression of a rare and unusually potent splice variant, VEGF
    Language English
    Publishing date 2017-02
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 231245-1
    ISSN 1432-136X ; 0174-1578
    ISSN (online) 1432-136X
    ISSN 0174-1578
    DOI 10.1007/s00360-016-1040-y
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    Uc I Zs.171: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  8. Article ; Online: Herpes Simplex Virus type 1 infects Langerhans cells and the novel epidermal dendritic cell, Epi-cDC2s, via different entry pathways.

    Bertram, Kirstie M / Truong, Naomi R / Smith, Jacinta B / Kim, Min / Sandgren, Kerrie J / Feng, Konrad L / Herbert, Jason J / Rana, Hafsa / Danastas, Kevin / Miranda-Saksena, Monica / Rhodes, Jake W / Patrick, Ellis / Cohen, Ralph C / Lim, Jake / Merten, Steven L / Harman, Andrew N / Cunningham, Anthony L

    PLoS pathogens

    2021  Volume 17, Issue 4, Page(s) e1009536

    Abstract: Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is ...

    Abstract Skin mononuclear phagocytes (MNPs) provide the first interactions of invading viruses with the immune system. In addition to Langerhans cells (LCs), we recently described a second epidermal MNP population, Epi-cDC2s, in human anogenital epidermis that is closely related to dermal conventional dendritic cells type 2 (cDC2) and can be preferentially infected by HIV. Here we show that in epidermal explants topically infected with herpes simplex virus (HSV-1), both LCs and Epi-cDC2s interact with HSV-1 particles and infected keratinocytes. Isolated Epi-cDC2s support higher levels of infection than LCs in vitro, inhibited by acyclovir, but both MNP subtypes express similar levels of the HSV entry receptors nectin-1 and HVEM, and show similar levels of initial uptake. Using inhibitors of endosomal acidification, actin and cholesterol, we found that HSV-1 utilises different entry pathways in each cell type. HSV-1 predominantly infects LCs, and monocyte-derived MNPs, via a pH-dependent pathway. In contrast, Epi-cDC2s are mainly infected via a pH-independent pathway which may contribute to the enhanced infection of Epi-cDC2s. Both cells underwent apoptosis suggesting that Epi-cDC2s may follow the same dermal migration and uptake by dermal MNPs that we have previously shown for LCs. Thus, we hypothesize that the uptake of HSV and infection of Epi-cDC2s will stimulate immune responses via a different pathway to LCs, which in future may help guide HSV vaccine development and adjuvant targeting.
    MeSH term(s) Adolescent ; Animals ; Cells, Cultured ; Child ; Child, Preschool ; Chlorocebus aethiops ; Epidermis/pathology ; Epidermis/virology ; HaCaT Cells ; HeLa Cells ; Herpes Simplex/pathology ; Herpes Simplex/virology ; Herpesvirus 1, Human/physiology ; Humans ; Infant ; Langerhans Cells/virology ; Signal Transduction/physiology ; Vero Cells ; Virus Internalization
    Language English
    Publishing date 2021-04-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7366
    ISSN (online) 1553-7374
    ISSN 1553-7366
    DOI 10.1371/journal.ppat.1009536
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: VEGF111: new insights in tissue invasion.

    Danastas, Kevin / Combes, Valery / Lindsay, Laura A / Grau, Georges E R / Thompson, Michael B / Murphy, Christopher R

    Frontiers in physiology

    2015  Volume 6, Page(s) 2

    Abstract: Vascular endothelial growth factor is a secreted glycoprotein that acts on endothelial cells to induce developmental and physiological angiogenesis. It has also been implicated in angiogenesis occurring in several pathologies, most notably, cancer. ... ...

    Abstract Vascular endothelial growth factor is a secreted glycoprotein that acts on endothelial cells to induce developmental and physiological angiogenesis. It has also been implicated in angiogenesis occurring in several pathologies, most notably, cancer. Alternative splicing of VEGF mRNA transcripts results in several isoforms with distinct properties depending on their exon composition. Recently, a new isoform has been identified, VEGF111 with a unique exon composition responsible for its high angiogenic potential. In humans, the only known inducer of VEGF111 is DNA damage but its natural presence in the uterus of the viviparous lizard, Saiphos equalis, suggests other mechanisms of regulation. Most interestingly, the possible relationship between the evolution of viviparity and the associated increased risk in developing cancer may be important in understanding the mechanisms underlying tumor development.
    Language English
    Publishing date 2015-01-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2015.00002
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