HSV-1 virions engineered for specific binding to cell surface receptors
HSV-1 virions engineered for specific binding to cell surface receptors
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DOI：
10.1016/j.ymthe.2003.12.010
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发表时间：
2004-03-01
影响因子：
12.4
通讯作者：
Breakefield, XO
中科院分区：
文献类型：
--
作者：
Grandi, P;Wang, S;Breakefield, XO
Expression of specific peptide epitopes on the surface of virions has significant potential for studying viral biology and designing vectors for targeted gene therapy. In this study, an HSV-1 amplicon plasmid expressing a modified glycoprotein C (gC), in which the heparan sulfate binding domain was replaced with a His-tag, was used in generating HSV-1 virions. Western blot analysis demonstrated the presence of modified gC in the purified virions. The amplicon vectors were packaged using a gC(-), lacZ(+) helper virus to generate a mixture of high-titer helper virus (lacZ(+)) and amplicon vectors (GFP(+)), which expressed modified gC in the virion envelope. His-tagged virions bound to 293 6H cells expressing a cell surface pseudo-His-tag receptor four-fold more efficiently than to parental 293 cells and also proved more effective than wild-type virus in binding to both cell types. Binding resulted in productive infection by the modified virions with expression of reporter genes and cytopathic effect comparable to those of wild-type virions. Thus, not only can HSV-1 tropism be manipulated to recognize a non-herpes simplex binding receptor, but it is also possible to increase the infective capacity of the vectors beyond that of the wild-type virus via specific ligand receptor combinations.
