title: Mutation of herpesvirus Saimiri ORF51 glycoprotein specifically targets infectivity to hepatocellular carcinoma cell lines.
abstract: Herpesvirus saimiri (HVS) is a gamma herpesvirus with several properties that make it an amenable gene therapy vector; namely its large packaging capacity, its ability to persist as a nonintegrated episome, and its ability to infect numerous human cell types. We used RecA-mediated recombination to develop an HVS vector with a mutated virion protein. The heparan sulphate-binding region of HVS ORF51 was substituted for a peptide sequence which interacts with somatostatin receptors (SSTRs), overexpressed on hepatocellular carcinoma (HCC) cells. HVS mORF51 showed reduced infectivity in non-HCC human cell lines compared to wild-type virus. Strikingly, HVS mORF51 retained its ability to infect HCC cell lines efficiently. However, neutralisation assays suggest that HVS mORF51 has no enhanced binding to SSTRs. Therefore, mutation of the ORF51 glycoprotein has specifically targeted HVS to HCC cell lines by reducing the infectivity of other cell types; however, the mechanism for this targeting is unknown.
authors.affiliation: Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Turrell
authors.forename: Adrian
authors.initials: A
authors.lastname: Whitehouse
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000235:genetics; D006497:Heparan Sulfate / Q000378:metabolism; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000821:virology*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D017481:Receptors, Somatostatin / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D017481:Receptors, Somatostatin; D014759:Viral Envelope Proteins; C491140:Orf51 protein, Herpesvirus saimiri; C101130:somatostatin receptor type 1