Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1

Johnson, Paul A.; Miyanohara, Atsushi; Levine, Fred; Cahill, Timothy C.; Friedmann, Theodore

doi:10.1128/jvi.66.5.2952-2965.1992

Cited by 281 publications

(75 citation statements)

References 84 publications

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“…At 3 and 6 hpi, the infected cells exhibited only chromosome uncoiling, with 87% of metaphases showing uncoiling in the region 1q12-21. An ICP4 deletion mutant (D30EBA) derived from HSV-1, also showed a similar pattern of chromosome aberrations [48]. As with the ts mutants, this ICP4 deletion mutant expresses all the other immediate early gene products except ICP4, but no early or late viral proteins.…”

Section: Herpes Simplex Interactions With the Cellular Genomementioning

confidence: 74%

Viral induction of site‐specific chromosome damage

Fortunato

Spector

2002

Reviews in Medical Virology

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The advent of advanced cell culture and cytogenetics techniques in the 1950s opened a new avenue for research on the pathogenic interactions between animal viruses and their hosts. Studies of many viruses revealed their ability to nonspecifically induce cytogenetic damage to their host cell's chromosomes. However, only three viruses, the oncogenic adenoviruses, herpes simplex virus (HSV) and human cytomegalovirus (HCMV), have been found to cause non-random, site-specific chromosomal damage. Adenovirus (Ad) type 12 induces fragility at four distinct loci (RNU1, RNU2, RN5S and PSU1) in many different types of human cells. A common feature of these loci is that they contain a repeated array of transcriptionally active genes encoding small structural RNAs. Site-specific induction of breaks also requires the virally encoded E1B protein of M(r) 55000 and the C-terminus of the cellular p53 protein. Analysis of the induction of damage by HSV and HCMV necessitates consideration of several factors, including the strain of virus used, the timing of infection, the type of cell used, and the multiplicity of infection. Both HSV strains 1 and 2 are cytotoxic, although the former seems to be more proficient at inducing damage. At early times post infection, HSV induces breaks and specific uncoiling of the centromeres of chromosomes 1, 9 and 16. This is followed at later times by a more complete severing of all of the chromosomes, termed pulverisation. Damage by HSV requires viral entry and de novo viral protein synthesis, with immediate early viral proteins responsible for the induction of breaks and uncoiling and early gene products (most likely nucleases) involved in the extensive pulverisation seen later. HCMV has been studied primarily in permissive human fibroblasts. Its ability to induce specific damage in chromosome 1 at two loci, 1q21 and 1q42, was only recently revealed as the cells must be in S-phase when they are infected for the breaks to be observed. In contrast to adenovirus and HSV, HCMV induction of specific breakage requires only viral entry into the cell and not de novo viral protein expression. This latter point may be a factor in its ability to cause damage in the developing fetal brain, where the most severe clinical manifestations of congenital infection are observed.

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Section: Herpes Simplex Interactions With the Cellular Genomementioning

confidence: 74%

Viral induction of site‐specific chromosome damage

Fortunato

Spector

2002

Reviews in Medical Virology

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“…helper virus is therefore also likely to cause at least BDNF at E7 (Biffo et al, 1995). In addition, chicken part of the effects seen in pHSVtrkA-and pHSVlacZcochleovestibular neurons isolated at E3.S hardly sur-infected cultures.…”

Section: Studying Neurotrophin Signaling By Hsv-1-mentioning

confidence: 98%

“…0087 (F.G.). A crucial issue when using amplicon vectors is to monitor potential cytotoxic effects caused by the virus REFERENCES (Johnson et al, 1992;Ho et al, 1995). During our Alonso M. T., Lim F., Nunez L., RepresaJ., Giraldez F., and Schimexperiments, we have not observed increased neuronal Neurochem., Vol.…”

Section: Studying Neurotrophin Signaling By Hsv-1-mentioning

confidence: 99%

Defining Responsiveness of Avian Cochlear Neurons to Brain‐Derived Neurotrophic Factor and Nerve Growth Factor by HSV‐1‐Mediated Gene Transfer

Garrido

Alonso

Lim

et al. 1998

Journal of Neurochemistry

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: The importance of individual members of the neurotrophin gene family for avian inner ear development is not clearly defined. Here we address the role of two neurotrophins, brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF), for innervation of the chicken cochlea. We have used defective herpes simplex virus type 1 (HSV‐1) vectors, or amplicons, to express these neurotrophins in dissociated cultures of cochlear neurons. HSV‐1‐mediated expression of BDNF promotes neuronal survival similar to the maximal level seen by exogenously added BDNF and exceeds its potency to produce neurite outgrowth. In contrast, cochlear neurons transduced with an amplicon producing bioactive NGF show no response. These results confirm BDNF as an important mediator of neurotrophin signaling inside avian cochlear neurons. However, these neurons can be rendered NGF‐responsive by transducing them with the high‐affinity receptor for NGF, TrkA. This study underlines the usefulness of amplicons to study and modify neurotrophin signaling inside neurons.

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“…HSV1-based vectors were initially examined as potential vehicles for gene transfer into the central nervous system. Un-wanted cytopathic effects resulting from viral infection plagued these early experiments (11,12). However, these cytopathic effects have subsequently been exploited to treat cancer.…”

mentioning

confidence: 99%

An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma

Yoon¹,

Nakamura²,

Carroll³

et al. 2000

FASEB j.

105

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Viruses used for gene therapy are usually genetically modified to deliver therapeutic transgenes and prevent viral replication. In contrast, replication-competent viruses may be used for cancer therapy because replication of some viruses within cancer cells can result in their destruction (oncolysis). Viral ribonucleotide reductase expression is defective in the HSV1 mutant hrR3. Cellular ribonucleotide reductase, which is scarce in normal liver and abundant in liver metastases, can substitute for its viral counterpart to allow hrR3 replication in infected cells. Two or three log orders more of hrR3 virions are produced from infection of colon carcinoma cells than from infection of normal hepatocytes in viral replication assays. This viral replication is oncolytic. A single intravascular administration of hrR3 into immune-competent mice bearing diffuse liver metastases dramatically reduces tumor burden. hrR3-mediated tumor inhibition is equivalent in immune-competent and immune-incompetent mice, suggesting that viral oncolysis and not the host immune response is the primary mechanism of tumor destruction. HSV1-mediated oncolysis of diffuse liver metastases is effective in mice preimmunized against HSV1. These results indicate that replication-competent HSV1 mutants hold significant promise as cancer therapeutic agents. Yoon, S. S., Nakamura, H., Carroll, N. M., Bode, B. P., Chiocca, E. A., Tanabe, K. K. An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma.

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Cytotoxicity of a replication-defective mutant of herpes simplex virus type 1

Abstract: Replication-defective mutants of herpes simplex virus type 1 (HSV-1) may prove useful as vectors for gene transfer, particularly to nondividing cells. CgalA3 is an immediate-early gene 3 (IE 3) deletion mutant of 2952

Cited by 281 publications

References 84 publications

Viral induction of site‐specific chromosome damage

Viral induction of site‐specific chromosome damage

Defining Responsiveness of Avian Cochlear Neurons to Brain‐Derived Neurotrophic Factor and Nerve Growth Factor by HSV‐1‐Mediated Gene Transfer

An oncolytic herpes simplex virus type 1 selectively destroys diffuse liver metastases from colon carcinoma

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