title: Herpes simplex virus type-1 (HSV-1) entry into human mesenchymal stem cells is heavily dependent on heparan sulfate.
abstract: Hematopoietic stem cells recipients remain susceptible to opportunistic viral infections including herpes simplex virus type-1 (HSV-1). The purpose of this investigation was to analyze susceptibility of human mesenchymal stem cells (hMSCs) to HSV-1 infection and identify the major entry receptor. Productive virus infection in hMSCs was confirmed by replication and plaque formation assays using a syncytial HSV-1 KOS (804) virus. To examine the significance of entry receptors, RT-PCR and antibody-blocking assays were performed. RT-PCR data showed the expression of gD receptors: nectin-1, 3-O sulfotransferase-3 (3-OST-3), and HVEM. Antibody-blocking assay together with heparinase treatment suggested an important role for HS and 3-O-sulfated heparan sulfate (3-OS HS), but not nectin-1 or HVEM, in mediating HSV-1 entry and spread in hMSCs. Taken together, our results provide strong evidence demonstrating that HSV-1 is capable of infecting hMSCs and HS and 3-OS HS serve as its entry receptors during this process.
authors.affiliation: Department of Basic Medical Sciences, College of Osteopathic Medicine 309 E, Western University of Health Sciences, Second Street, Pomona, CA 91766, USA.
authors.forename: Samiksha
authors.initials: S
authors.lastname: Choudhary
authors.forename: Maribel
authors.initials: M
authors.lastname: Marquez
authors.forename: Frances
authors.initials: F
authors.lastname: Alencastro
authors.forename: Frank
authors.initials: F
authors.lastname: Spors
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D003599:Cytoskeleton / Q000378:metabolism; D015726:Giant Cells; D006367:HeLa Cells; D006497:Heparan Sulfate / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000821:virology*; D008856:Microscopy, Fluorescence; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000378:metabolism; D010948:Viral Plaque Assay; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology
chemical_list: D015815:Cell Adhesion Molecules; D006497:Heparan Sulfate; D000075983:Nectins; D053240:Receptors, Tumor Necrosis Factor, Member 14; D014759:Viral Envelope Proteins; C000619010:NECTIN1 protein, human; C506028:TNFRSF14 protein, human; C039447:glycoprotein D, Human herpesvirus 1