Engineered herpes simplex virus 1 is dependent on IL13Rα2 receptor for cell entry and independent of glycoprotein D receptor interaction

Specific targeted binding of herpes simplex virus type 1 to hepatocytes via the human hepatitis B virus preS1 peptide

“…11 In another report, a mutant virus, deleted for the HS binding domains of gB and gC, and deleted for the HveA binding site of gD was reported to encode and incorporate a gC:IL13 fusion protein, which gave the mutant virus the ability to bind to IL13Ra2 receptor-bearing cells. 58 Nevertheless, this mutant virus is still displaying the affinity for the HveC gD receptor.…”

A strategy for systemic delivery of the oncolytic herpes virus HSV1716: redirected tropism by antibody-binding sites incorporated on the virion surface as a glycoprotein D fusion protein

“…31,32,34 Infection of a hepatoblastoma cell line by viruses in which the human hepatitis B virus hepatocyte-binding preS1 protein or its minimally active peptide respectively replaced gC amino acids (aa) 149-213 or 149-442 was blocked by anti-preS1 antibodies and replacing the heparan sulphate-binding region of gC with a 6-His tag improved virus binding to permissive 293 cells expressing a pseudo-His-tag receptor. 33,35 Initially, we analysed the suitability of various glycoprotein D fragments to direct the incorporation of N terminally fused scFv into the HSV-1 envelope and, assessed the abilities of incorporated fusion proteins to alter the tropism of the virus.…”

“…[23][24][25][26][27][28][29] Results from a number of studies with HSV-1 have shown that it is possible to alter the tropism by incorporating ligands such as erythropoietin, interleukin (IL) 13, human hepatitis B virus preS1 peptide, the N-terminal fragment of urokinase-type plasminogen activator or 6-His into the viral envelope as glycoprotein fusion proteins. [30][31][32][33][34][35] Targeting has also been achieved using a soluble adapter molecule comprising an antiepidermal growth factor receptor (EGFR) scFv linked to the HSV-1 gD-binding domain of nectin-1 and more recently, a scFv against HER2/neu incorporated into the N terminus of gD has been shown to redirect the tropism of HSV-1 to this mammary tumour receptor. 36,37 Initiation of infection by HSV-1 requires cells to display the appropriate receptors to permit viral access, a process requiring the complex interplay of a number of cellular and viral membrane components.…”

Replication-competent herpes simplex vectors: design and applications

“…Simultaneously, efforts are in progress to modify gD, the other glycoprotein involved in HSV-1 binding and penetration into the host cell. 63,64 In a recent report, the R5111 mutant virus was described lacking the HS binding domains of gB, and in which the HS and HVEM-binding regions of gC and gD were substituted with IL13-coding sequences. HSV-1 R5111 can infect J13R cells containing the IL13Ra2 receptor and lacking all other HSV-1 receptors.…”

“…However, this mutant still retains the other gD-binding affinities, and it is not yet established whether it can productively infect the target cells, in a similar way to that obtained with wt HSV. 64 An alternative approach reports a transiently vesicular stomatitis virus glycoprotein G (VSV-G) pseudotyped gD minus HSV-1, but to date a stable mutant has not been reported. 63 A further stimulus to the search of new strategies to alter HSV cell tropism derives from a recent observation that selected mutations in gD can reduce or abolish entry/fusion activity with nectin-1 and nectin-2, the principal receptors for HSV-1 entry into neurons, without preventing the activity of HVEM or 3-0-S HS that alternatively, can mediate entry into T cells and fibroblasts.…”