Herpes simplex virus 1 recombinant virions exhibiting the amino terminal fragment of urokinase-type plasminogen activator can enter cells via the cognate receptor.
Earlier this laboratory constructed a herpes simplex virus 1 recombinant (R5111) that carries a IL13 ligand inserted into glycoprotein D and can enter cells via the IL13Ralpha2 receptor commonly expressed on the surface of malignant glioma cells. In this report, we describe the properties of two recombinant viruses carrying chiemric gD genes. In R5181 recombinant virus the chimeric gene consisted on the residues 20-155 of urokinase plaminogen activator (uPA) inserted between residues 24 and 25 of gD. In R5182 the insert consisted of a 23-residue sequence encoding the uPA binding domain for the urokinase plaminogen activator receptor (uPAR). These viruses were constructed for three reasons, to increase the number of viruses that specifically target receptors on the surface of malignant glioma cells, to determine whether viruses exhibiting novel ligands could enter cells via receptors anchored to the cell surface via glycosylphosphatidylinositol anchor as has been recently demonstrated for nectin1, and to determine whether receptors other than IL13Ralpha2 could be targeted by genetic engineering of the virus. We report that R5181 but not R5182 recombinant virus was able to enter cells expressing uPAR. The results indicate that HSV-1 recombinant viruses can be engineered to enter cells via a variety of unrelated nonviral receptors, including receptors that are anchored to the cells surface but without transmembrane domains.
Kamiyama
H
H
The Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL 60637, USA.
Zhou
G
G
Roizman
B
B
D000595:Amino Acid Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D002460:Cell Line; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000378:metabolism; D005910:Glioma / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D050130:Oncolytic Virotherapy / Q000379:methods*; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D014614:Vaccines, Synthetic / Q000627:therapeutic use; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014765:Viral Vaccines / Q000627:therapeutic use; D014771:Virion; D014779:Virus Replication
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1; D014568:Urokinase-Type Plasminogen Activator