The RL neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency

Maclean, Alasdair; Robertson, L M; McKay, E. M.; Brown, Stuart A.

doi:10.1099/0022-1317-72-9-2305

Cited by 16 publications

(17 citation statements)

References 15 publications

(5 reference statements)

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“…HSV type 1 (HSV-1) mutants that fail to express the ␥ 1 34.5 protein are incapable of multiplying and causing encephalitis in experimental animal models (18,35,48). Similar phenotypes have been observed for HSV-2 mutants lacking the ␥ 1 34.5 gene (34,38).…”

mentioning

confidence: 48%

“…The triplet repeats are a constant feature of the ␥ 1 34.5 protein in HSV-1, but the number of repeats varies among different strains (6, 21). The number of triplet repeats in the ␥ 1 34.5 protein appears to affect the ability of HSV to invade the central nervous system from the peripheral tissue (6, 37). However, the triplet repeats are not present in the ␥ 1 34.5 protein of HSV-2 (38).…”

mentioning

confidence: 99%

“…Following primary infection, HSV establishes a latent infection or lytic infection in which viruses undergo transcription, replication, assembly, and egress. While many viral factors are involved in this complex process, the ␥ 1 34.5 protein has been demonstrated to be a critical determinant of virus infection (18). Several lines of evidence indicate that the ␥ 1 34.5 protein contributes to HSV virulence in vivo (18,34,35,46,48).…”

mentioning

confidence: 99%

“…While many viral factors are involved in this complex process, the ␥ 1 34.5 protein has been demonstrated to be a critical determinant of virus infection (18). Several lines of evidence indicate that the ␥ 1 34.5 protein contributes to HSV virulence in vivo (18,34,35,46,48). HSV type 1 (HSV-1) mutants that fail to express the ␥ 1 34.5 protein are incapable of multiplying and causing encephalitis in experimental animal models (18,35,48).…”

mentioning

confidence: 99%

“…In HSV-1, the ␥ 1 34.5 gene encodes a protein of 263 amino acids consisting of an amino-terminal domain, a linker region of three-amino-acid repeats (Ala-Thr-Pro), and a carboxyl-terminal domain (21). The triplet repeats are a constant feature of the ␥ 1 34.5 protein in HSV-1, but the number of repeats varies among different strains (6, 21).…”

mentioning

confidence: 99%

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Replication of Herpes Simplex Virus 1 Depends on the γ ₁ 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection

Jing

Cerveny

Yang

et al. 2004

J Virol

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The ability of the ␥ 1 34.5 protein to suppress the PKR response plays a crucial role in herpes simplex virus pathogenesis. In this process, the ␥ 1 34.5 protein associates with protein phosphatase 1 to form a large complex that dephosphorylates eIF-2␣ and thereby prevents translation shutoff mediated by PKR. Accordingly, ␥ 1 34.5 null mutants are virulent in PKR-knockout mice but not in wild-type mice. However, ␥ 1 34.5 deletion mutants, with an extragenic compensatory mutation, inhibit PKR activity but remain avirulent, suggesting that the ␥ 1 34.5 protein has additional functions. Here, we show that a substitution of the ␥ 1 34.5 gene with the NS1 gene from influenza A virus renders viral resistance to interferon involving PKR. The virus replicates as efficiently as wild-type virus in SK-N-SH and CV-1 cells. However, in mouse 3T6 cells, the virus expressing the NS1 protein grows at an intermediate level between the wild-type virus and the ␥ 1 34.5 deletion mutant. This decrease in growth, compared to that of the wild-type virus, is due not to an inhibition of viral protein synthesis but rather to a block in virus release or egress. Virus particles are predominantly present in the nucleus and cytoplasm. Notably, deletions in the amino terminus of the ␥ 1 34.5 protein lead to a significant decrease in virus growth in mouse 3T6 cells, which is independent of eIF-2␣ dephosphorylation. In correlation, a series of deletions in the amino-terminal domain impair nuclear as well as cytoplasmic egress. These results indicate that efficient viral replication depends on the ␥ 1 34.5 functions required to prevent the PKR response and to facilitate virus egress in the different stages during virus infection.

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confidence: 48%

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confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Replication of Herpes Simplex Virus 1 Depends on the γ ₁ 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection

Jing

Cerveny

Yang

et al. 2004

J Virol

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Treatment of Spontaneously Arising Retinoblastoma Tumors in Transgenic Mice with an Attenuated Herpes Simplex Virus Mutant

et al. 1997

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The use of viruses to treat tumors has received renewed interest with the availability of genetically defined attenuated mutants. Herpes simplex virus (HSV) type 1 in particular has been shown to be effective for tumors of neuronal origin. However, the model systems used for these studies rely on the use of explanted tumor cells in immunodeficient animals. We have used a recently developed transgenic mouse model, wherein mice spontaneously develop retinoblastomas, to determine if a mutant HSV has a therapeutic effect against an endogenously arising tumor in an immunocompetent host. The injection of 1 x 10(6) PFU of the neuroattenuated HSV-1/HSV-2 recombinant RE6 into the vitreous of transgenic mice resulted in a significant inhibition of tumor growth compared to injection of medium alone (P = 0.0063). Immunohistochemical analysis of viral antigen showed that viral replication was restricted to focal areas of the tumors and the retinal pigment epithelium. Viral growth was not significantly different in the eyes of transgene-positive and transgene-negative mice, suggesting that enhanced replication in tumor cells may not explain the effects. Tumor cells in the treated eyes were significantly less differentiated than those in the untreated eyes (P = 0.04), suggesting that the virus may replicate better in certain cell types in the tumors. Although the injection of RE6 resulted in a difference in tumor size, the treatment did not result in the elimination of tumors in any of the mice improvements in the efficacy of tumor control are needed if this therapy is to be of use.

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Construction and Characterization of an Oncolytic HSV Vector Containing a Fusogenic Glycoprotein and Prodrug Activation for Enhanced Local Tumor Control

Simpson

Coffin

2009

Gene Therapy of Cancer

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A large number of oncolytic viral vectors are currently under clinical development for cancer therapy. Herpes simplex virus type 1 (HSV-1) has demonstrated particular promise in this field, showing genetically engineered selective tumor replication and cytotoxicity in a wide variety of tumor types, without damaging healthy tissues. Enhanced activity has been observed when a range of therapeutic genes has been inserted into various oncolytic HSV genomes. Here, we discuss methods used to develop and characterize an oncolytic HSV virus that combines expression of a highly potent prodrug activating gene (yeast cytosine deaminase/uracil phosphoribosyltransferase fusion [Fcy::Fur]) and the fusogenic glycoprotein from gibbon ape leukemia virus (GALV) for enhanced local tumor control.

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The RL neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency

Cited by 16 publications

References 15 publications

Replication of Herpes Simplex Virus 1 Depends on the γ ₁ 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection

Replication of Herpes Simplex Virus 1 Depends on the γ ₁ 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection

Treatment of Spontaneously Arising Retinoblastoma Tumors in Transgenic Mice with an Attenuated Herpes Simplex Virus Mutant

Construction and Characterization of an Oncolytic HSV Vector Containing a Fusogenic Glycoprotein and Prodrug Activation for Enhanced Local Tumor Control

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The RL neurovirulence locus in herpes simplex virus type 2 strain HG52 plays no role in latency

Cited by 16 publications

References 15 publications

Replication of Herpes Simplex Virus 1 Depends on the γ 1 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection

Replication of Herpes Simplex Virus 1 Depends on the γ 1 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection

Treatment of Spontaneously Arising Retinoblastoma Tumors in Transgenic Mice with an Attenuated Herpes Simplex Virus Mutant

Construction and Characterization of an Oncolytic HSV Vector Containing a Fusogenic Glycoprotein and Prodrug Activation for Enhanced Local Tumor Control

Contact Info

Product

Resources

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Replication of Herpes Simplex Virus 1 Depends on the γ ₁ 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection

Replication of Herpes Simplex Virus 1 Depends on the γ ₁ 34.5 Functions That Facilitate Virus Response to Interferon and Egress in the Different Stages of Productive Infection