The JH2604 deletion variant of herpes simplex virus type 2 (HG52) fails to produce necrotizing encephalitis following intracranial inoculation of mice

Taha, M Y; Brown, Stuart A.; Clements, G. B.; Graham, David I.

doi:10.1099/0022-1317-71-7-1597

Cited by 19 publications

(10 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Talimogene laherparepvec is also deleted for the gene encoding ICP47, which blocks antigen presentation to major histocompatibility complex class 1 and 2 molecules, and has the coding sequence for human granulocytemacrophage colony-stimulating factor (GM-CSF) inserted in the place of ICP34.5. HSV1716 is incapable of replicating in the central nervous system (6)(7)(8) and has been extensively characterized both in vitro and in vivo. It maintains expression of thymidine kinase, targetable by administration of acyclovir, thereby providing a "therapeutic safety net" in the unusual circumstance of viral replication escape and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients

Streby

Geller

Currier

et al. 2017

Clinical Cancer Research

116

View full text Add to dashboard Cite

Purpose: HSV1716 is an oncolytic herpes simplex virus-1 (HSV-1) studied in adults via injection into the brain and superficial tumors. To determine the safety of administering HSV1716 to pediatric patients with cancer, we conducted a phase I trial of image-guided injection in young patients with relapsed or refractory extracranial cancers.Experimental Design: We delivered a single dose of 10 5 to 10 7 infectious units of HSV1716 via computed tomography-guided intratumoral injection and measured tumor responses by imaging. Patients were eligible for up to three more doses if they achieved stable disease. We monitored HSV-1 serum titers and shedding by PCR and culture.Results: We administered a single dose of HSV1716 to eight patients and two doses to one patient. We did not observe any dose-limiting toxicities. Adverse events attributed to virus included low-grade fever, chills, and mild cytopenias. Six of eight HSV-1 seronegative patients at baseline showed seroconversion on day 28. Six of nine patients had detectable HSV-1 genomes by PCR in peripheral blood appearing on day þ4 consistent with de novo virus replication. Two patients had transient focal increases in metabolic activity on 18 fluorinedeoxyglucose PET, consistent with inflammatory reactions. In one case, the same geographic region that flared later appeared necrotic on imaging. No patient had an objective response to HSV1716.Conclusions: Intratumoral HSV1716 is safe and well-tolerated without shedding in children and young adults with late-stage, aggressive cancer. Viremia consistent with virus replication and transient inflammatory reactions hold promise for future HSV1716 studies. Clin Cancer Res; 1-9. Ó2017 AACR.

show abstract

Section: Introductionmentioning

confidence: 99%

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients

Streby

Geller

Currier

et al. 2017

Clinical Cancer Research

116

View full text Add to dashboard Cite

show abstract

“…Variants of HSV in which RL1 is deleted or mutated have been reported to be incapable of replicating in the CNS of mice and causing encephalitis (Chou et al, 1990 ;MacLean et al, 1991 ;Taha et al, 1990). From these and other studies, it was speculated that the replication of HSV-1 ICP34.5 mutants may be cell cycle dependent, thereby rendering these mutants incapable of replication in post-mitotic and\or quiescent cells in the brain Chou et al, 1990 ;Kesari et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

A neuroattenuated ICP34.5-deficient herpes simplex virus type 1 replicates in ependymal cells of the murine central nervous system.

Kesari

Lasner

Balsara

et al. 1998

Journal of General Virology

View full text Add to dashboard Cite

“…Dolan, E. McKie, A. R. MacLean & D. J. McGeoch, unpublished data), adding a further gene to the complement recognized for strain 17. ICP34.5 appears to be an important determinant of viral neurovirulence in HSV-1 , and in HSV-2 a neurovirulence determinant maps to an equivalent region of the genome (Taha et al, 1989a(Taha et al, , b, 1990.…”

Section: Introductionmentioning

confidence: 99%

Comparative Sequence Analysis of the Long Repeat Regions and Adjoining Parts of the Long Unique Regions in the Genomes of Herpes Simplex Viruses Types 1 and 2

McGeoch

Cunningham

McIntyre

et al. 1991

Journal of General Virology

150

118

View full text Add to dashboard Cite

We report the determination of the DNA sequence of the long repeat (RL) region and adjacent parts of the long unique (UL) region in the genome of herpes simplex virus type 2 (HSV-2) strain HG52. The DNA sequences and genetic content of the extremities of HSV-2 UL were found to be closely similar to those determined previously for HSV-1. The 5658 bp sequenced at the left end of HSV-2 UL contained coding regions for genes UL1 to UL4 plus part of UL5. The 4355 bp sequenced at the right end Of UL contained coding regions for part of gene UL53, and the whole of genes UL54 to UL56. Comparison of the HSV-1 and HSV-2 UL56 sequences led to a correction in the published HSV-1 UL56 reading frame. The HSV-2 R L region, including one copy of the a sequence, was determined to be 9263 bp, with a base composition of 75-4% G+C and with many repetitive sequence elements. In HSV-2 RL, sequences were identified corresponding to HSV-1 genes encoding the immediate early IE110 (ICP0) transcriptional regulator and the ICP34.5 neurovirulence factor; the former HSV-2 gene was proposed to contain two introns, and the latter one intron. Downstream of the HSV-2 immediate early gene, the RE sequence encoding the latency-associated transcripts (LATs) was found to be dissimilar to that in HSV-1; the probable LAT promoter regions, however, showed similarities to HSV-1. Properties of the LAT sequences in both HSV-1 and HSV-2 were consistent with LATs being generated as an intron excised from a longer transcript.

show abstract

The JH2604 deletion variant of herpes simplex virus type 2 (HG52) fails to produce necrotizing encephalitis following intracranial inoculation of mice

Cited by 19 publications

References 14 publications

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients

Intratumoral Injection of HSV1716, an Oncolytic Herpes Virus, Is Safe and Shows Evidence of Immune Response and Viral Replication in Young Cancer Patients

A neuroattenuated ICP34.5-deficient herpes simplex virus type 1 replicates in ependymal cells of the murine central nervous system.

Comparative Sequence Analysis of the Long Repeat Regions and Adjoining Parts of the Long Unique Regions in the Genomes of Herpes Simplex Viruses Types 1 and 2

Contact Info

Product

Resources

About