scholarly journals Nectin-1 Expression Correlates with the Susceptibility of Malignant Melanoma to Oncolytic Herpes Simplex Virus In Vitro and In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3058
Author(s):  
Barbara Schwertner ◽  
Georg Lindner ◽  
Camila Toledo Toledo Stauner ◽  
Elisa Klapproth ◽  
Clara Magnus ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Intralesional Injection ◽  
Surface Receptors ◽  
Oncolytic Herpes Simplex Virus ◽  
Simplex Virus ◽  
Oncolytic Activity

Talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus, is approved for intralesional injection of unresectable stage IIIB/IVM1a melanoma. However, it is still unclear which parameter(s) predict treatment response or failure. Our study aimed at characterizing surface receptors Nectin-1 and the herpes virus entry mediator (HVEM) in addition to intracellular molecules cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) as potential bio-markers for oncolytic virus treatment. In 20 melanoma cell lines, oncolytic activity of T-VEC was correlated with the expression of Nectin-1 but not HVEM, as evaluated via flow cytometry and immunohistochemistry. Knockout using CRISPR/Cas9 technology confirmed the superior role of Nectin-1 over HVEM for entry and oncolytic activity of T-VEC. Neither cGAS nor STING as evaluated by Western Blot and immunohistochemistry correlated with T-VEC induced oncolysis. The role of these biomarkers was retrospectively analyzed for the response of 35 cutaneous melanoma metastases of 21 patients to intralesional T-VEC injection, with 21 (60.0%) of these lesions responding with complete (n = 16) or partial regression (n = 5). Nectin-1 expression in pretreatment biopsies significantly predicted treatment outcome, while the expression of HVEM, cGAS, and STING was not prognostic. Altogether, Nectin-1 served as biomarker for T-VEC-induced melanoma regression in vitro and in vivo.

scholarly journals Oncolytic herpes simplex virus infects myeloma cells in vitro and in vivo

2021 ◽  
Vol 20 ◽  
pp. 519-531
Author(s):  
Jayeeta Ghose ◽  
Ada Dona ◽  
Mariam Murtadha ◽  
Emine Gulsen Gunes ◽  
Enrico Caserta ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Myeloma Cells ◽  
Oncolytic Herpes Simplex Virus ◽  
Simplex Virus

Oncolytic Herpes Simplex Virus Decreased Rhabdomyosarcoma Cell Survival In Vitro and In Vivo

2015 ◽  
Vol 221 (4) ◽  
pp. S105-S106
Author(s):  
Alicia M. Waters ◽  
Jerry Stewart ◽  
Gregory K. Friedman ◽  
G.Y. Gillespie ◽  
James M. Markert ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Survival ◽  
Oncolytic Herpes Simplex Virus ◽  
Rhabdomyosarcoma Cell ◽  
Simplex Virus

scholarly journals Immediate-Early Expression of the Herpes Simplex Virus Type 1 ICP27 Transcript Is Not Critical for Efficient Replication In Vitro or In Vivo

2004 ◽  
Vol 78 (19) ◽  
pp. 10470-10478 ◽  
Author(s):  
Aixu Sun ◽  
G. V. Devi-Rao ◽  
M. K. Rice ◽  
L. W. Gary ◽  
D. C. Bloom ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immediate Early ◽  
Wild Type ◽  
Early Expression ◽  
Simplex Virus

ABSTRACT We constructed a promoter mutation altering the immediate-early expression of the herpes simplex virus type 1 (HSV-1) ICP27 transcript and its cognate wild-type rescue viruses in order to assess the role of the ICP27 protein in the earliest stages of viral infection by global transcriptional analysis with a DNA microarray. This mutant, ICP27/VP16, replaces the whole ICP27 promoter/enhancer with the VP16 promoter. It demonstrates loss of immediate-early expression of ICP27 according to the criteria expression in the absence of de novo protein synthesis and earliest expression in the kinetic cascade. Significant differences in relative transcript abundances between the mutant and wild-type rescue viruses were limited at the earliest times measured and not evident at all by 4 h after infection. Consistent with this observation, levels of some critical proteins were reduced in the mutant as compared to rescue virus infections at the earliest times tested, but were equivalent by 8 h postinfection. Further, both single and multistep levels of virus replication were equivalent with both mutant and rescue viruses. Thus, altering the immediate-early kinetics of ICP27 leads to a suboptimal quantitative lag phase in gene expression but without consequence for replication fitness in vitro. Infections in vivo also revealed equivalent ability of mutant and rescue viruses to invade the central nervous system of mice following footpad injections. Limitations to an immediate-early role of ICP27 in the biology of HSV are discussed in light of these observations.

scholarly journals Structural Variability of the Herpes Simplex Virus 1 GenomeIn VitroandIn Vivo

2012 ◽  
Vol 86 (16) ◽  
pp. 8592-8601 ◽  
Author(s):  
Charlotte Mahiet ◽  
Ayla Ergani ◽  
Nicolas Huot ◽  
Nicolas Alende ◽  
Ahmed Azough ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Considerable Proportion ◽  
Inverted Repeats ◽  
Herpes Simplex Virus 1 ◽  
Cell Extracts ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus 1 (HSV-1) is a human pathogen that leads to recurrent facial-oral lesions. Its 152-kb genome is organized in two covalently linked segments, each composed of a unique sequence flanked by inverted repeats. Replication of the HSV-1 genome produces concatemeric molecules in which homologous recombination events occur between the inverted repeats. This mechanism leads to four genome isomers (termed P, IS, IL, and ILS) that differ in the relative orientations of their unique fragments. Molecular combing analysis was performed on DNA extracted from viral particles and BSR, Vero, COS-7, and Neuro-2a cells infected with either strain SC16 or KOS of HSV-1, as well as from tissues of experimentally infected mice. Using fluorescence hybridization, isomers were repeatedly detected and distinguished and were accompanied by a large proportion of noncanonical forms (40%). In both cell and viral-particle extracts, the distributions of the four isomers were statistically equivalent, except for strain KOS grown in Vero and Neuro-2a cells, in which P and IS isomers were significantly overrepresented. In infected cell extracts, concatemeric molecules as long as 10 genome equivalents were detected, among which, strikingly, the isomer distributions were equivalent, suggesting that any such imbalance may occur during encapsidation.In vivo, for strain KOS-infected trigeminal ganglia, an unbalanced distribution distinct from the onein vitrowas observed, along with a considerable proportion of noncanonical assortment.

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