المؤلفون: Calle, A., Morfin, F., Thouvenot, D., Greco, A., Cayre, M., Kindbeiter, K., Martin, L., Levillain, O., Diaz, Jj

المساهمون: Biologie et Pathologie des Communications Cellulaires Dans les Glandes Endocrines, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie et pathogenèse virale (VPV), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie, Hospices Civils de Lyon (HCL), NMDA : Neurogenèse et morphogenèse dans le développement et chez l'adulte (NNMDDCA), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), IDEALP-pharma, Villeurbanne, Physiopathologie Metabolique et Renale, This work was supported by CNRS, INSERM, and Université Claude Bernard Lyon-1. We are grateful to H. Marsden (MRC, Glasgow, UK) for the generous gift of anti-ICP27 and anti-UL42 antibodies, and to Roger Augier and Simone Lambert for technical assistance. We thank R. W. Currie for critical reading of the manuscript.

المصدر: ISSN: 0892-6638.

مصطلحات موضوعية: Acyclovir/pharmacology, Adenosylmethionine Decarboxylase/*antagonists & inhibitors/genetics, Antiviral Agents/*pharmacology, Cell Line, Cell Proliferation/drug effects, Enzyme Inhibitors/*pharmacology/therapeutic use, Foscarnet/pharmacology, Gene Expression Regulation, Enzymologic, Herpes Simplex/*drug therapy/enzymology, Herpesvirus 1, Human/*drug effects/physiology, Humans, Mitoguazone/*pharmacology, RNA, Messenger/analysis, Spermine/metabolism/pharmacology, Virus Replication/drug effects, OCIS 000.1430, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology

الوصف: All the available antiherpetic drugs are directed against viral proteins. Their extensive clinical use has led to the emergence of resistant viral strains. There is a need for the treatment of herpes infections due to resistant strains, especially for immunocompromised patients. To design new kinds of drugs, we have developed a strategy to identify cellular targets. Herpes simplex virus type 1 (HSV-1) infection is concomitant to a repression of most host protein synthesis. However, some cellular proteins continue to be efficiently synthesized. We speculated that some of them could determine the outcome of infection. Since two polyamines, spermidine and spermine, are components of the HSV-1 virions, we investigated whether enzymes involved in their synthesis could be required for viral infection. We show that inhibition of S-adenosyl methionine decarboxylase, a key enzyme of the polyamine metabolic pathway, prevents HSV-1 infection. Inhibition of polyamine synthesis prevents infection of culture cells with HSV-1 laboratory strains as well as clinical isolates that are resistant to the conventional antiviral drugs acyclovir and foscarnet. Our data provide the opportunity to develop molecules with a novel mechanism of action for the treatment of herpes infection.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/15863396; hal-00124242; https://hal.science/hal-00124242Test; PUBMED: 15863396

الإتاحة: https://hal.science/hal-00124242Test

المؤلفون: Olivier Levillain, Florence Morfin, Aleth Callé, Myriam Cayre, Jean-Jacques Diaz, Laetitia Martin, Karine Kindbeiter, Danielle Thouvenot, Anna Greco

المساهمون: Biologie et Pathologie des Communications Cellulaires Dans les Glandes Endocrines, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Virologie et pathogenèse virale (VPV), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie, Hospices Civils de Lyon (HCL), NMDA : Neurogenèse et morphogenèse dans le développement et chez l'adulte (NNMDDCA), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), IDEALP-pharma, Villeurbanne, Physiopathologie Metabolique et Renale, This work was supported by CNRS, INSERM, and Université Claude Bernard Lyon-1. We are grateful to H. Marsden (MRC, Glasgow, UK) for the generous gift of anti-ICP27 and anti-UL42 antibodies, and to Roger Augier and Simone Lambert for technical assistance. We thank R. W. Currie for critical reading of the manuscript., Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2

المصدر: FASEB Journal
FASEB Journal, 2005, pp.1130
FASEB Journal, Federation of American Society of Experimental Biology, 2005, 19 (9), pp.1128-30. ⟨10.1096/fj.04-2108fje⟩
FASEB Journal, Federation of American Society of Experimental Biology, 2005, pp.1130

مصطلحات موضوعية: Foscarnet, Enzymologic, Mitoguazone, viruses, Spermine, Acyclovir, MESH: Herpes Simplex, Herpesvirus 1, Human, MESH: Mitoguazone, medicine.disease_cause, Virus Replication, Biochemistry, Enzyme Inhibitors/*pharmacology/therapeutic use, Spermine/metabolism/pharmacology, Cell Proliferation/drug effects, chemistry.chemical_compound, Foscarnet/pharmacology, MESH: Acyclovir, S-Adenosyl methionine, MESH: Spermine, Enzyme Inhibitors, OCIS 000.1430, 0303 health sciences, Methionine decarboxylase, MESH: Gene Expression Regulation, Enzymologic, Antiviral Agents/*pharmacology, 3. Good health, Messenger/analysis, MESH: Herpesvirus 1, Human, MESH: Enzyme Inhibitors, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine.symptom, Biotechnology, medicine.drug, MESH: Foscarnet, MESH: Antiviral Agents, Adenosylmethionine Decarboxylase, Herpes Simplex/*drug therapy/enzymology, Mitoguazone/*pharmacology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Antiviral Agents, Gene Expression Regulation, Enzymologic, Cell Line, 03 medical and health sciences, MESH: Cell Proliferation, Genetics, medicine, Humans, RNA, Messenger, Molecular Biology, 030304 developmental biology, Cell Proliferation, MESH: RNA, Messenger, MESH: Adenosylmethionine Decarboxylase, Virus Replication/drug effects, MESH: Humans, 030306 microbiology, Herpesvirus 1, MESH: Virus Replication, Herpes Simplex, Adenosylmethionine Decarboxylase/*antagonists & inhibitors/genetics, Virology, MESH: Cell Line, Spermidine, Herpes simplex virus, chemistry, Mechanism of action, Gene Expression Regulation, Human/*drug effects/physiology, RNA, Acyclovir/pharmacology, Polyamine

الوصف: All the available antiherpetic drugs are directed against viral proteins. Their extensive clinical use has led to the emergence of resistant viral strains. There is a need for the treatment of herpes infections due to resistant strains, especially for immunocompromised patients. To design new kinds of drugs, we have developed a strategy to identify cellular targets. Herpes simplex virus type 1 (HSV-1) infection is concomitant to a repression of most host protein synthesis. However, some cellular proteins continue to be efficiently synthesized. We speculated that some of them could determine the outcome of infection. Since two polyamines, spermidine and spermine, are components of the HSV-1 virions, we investigated whether enzymes involved in their synthesis could be required for viral infection. We show that inhibition of S-adenosyl methionine decarboxylase, a key enzyme of the polyamine metabolic pathway, prevents HSV-1 infection. Inhibition of polyamine synthesis prevents infection of culture cells with HSV-1 laboratory strains as well as clinical isolates that are resistant to the conventional antiviral drugs acyclovir and foscarnet. Our data provide the opportunity to develop molecules with a novel mechanism of action for the treatment of herpes infection.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac2f0e2f07324816b9b9d92df6cc5087Test
https://hal.science/hal-00124242Test