Herpes Simplex Virus Type 1 Penetrates the Basement Membrane in Human Nasal Respiratory Mucosa 英文参考文献.docVIP

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Herpes Simplex Virus Type 1 Penetrates the Basement Membrane in Human Nasal Respiratory Mucosa 英文参考文献.doc

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Herpes Simplex Virus Type 1 Penetrates the Basement Membrane in Human Nasal Respiratory Mucosa 英文参考文献

HerpesSimplexVirusType1PenetratestheBasement MembraneinHumanNasalRespiratoryMucosa SarahGlorieux1*,ClausBachert2,HermanW.Favoreel1,3,AnneliesP.Vandekerckhove1 ,Lennert Steukers1,AnamariaRekecki4,WimVandenBroeck4,JolineGoossens5,SiskaCroubels5,ReginaldF. Clayton6,HansJ.Nauwynck1 1LaboratoryofVirology,FacultyofVeterinaryMedicine,GhentUniversity,Merelbeke,Belgium,2DepartmentofOtorhinolaryngology,UniversityHospitalGhent,Ghent, Belgium, 3Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium, 4Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium, 5Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke,Belgium,6TibotecBVBA,Beerse,Belgium Abstract Background: Herpes simplex virus infections are highly prevalent in humans. However, the current therapeutics suffer important drawbacks such as limited results in neonates, increasing occurrence of resistance and impeded treatment of stromal infections. Remarkably, interactions of herpesviruses with human mucosa, the locus of infection, remain poorly understoodandtheunderlyingmechanismsinstromalinfectionremaincontroversial. Methodology/Principal Findings: A human model consisting of nasal respiratory mucosa explants was characterised. Viabilityandintegritywereexaminedduring96hofcultivation.HSV1-mucosainteractionswereanalysed.Inparticular,we investigatedwhetherHSV1isabletoreachthestroma. Explantviabilityandintegrityremainedpreserved.HSV1induced roundingupandlooseningofepithelialcells withveryfewapoptotic andnecroticcellsobserved.Following 16–24hof infection,HSV1penetratedthebasementmembraneandreplicatedintheunderlyinglaminapropria. Conclusions/Significance: This human explant model can be used to study virus-mucosa interactions and viral mucosal invasionmechanisms.Usingthismodel,ourresultsprovideanovelinsightintotheHSV1stromalinvasionmechanismand forthefirsttimedirectlydemonst