Trigeminal Ganglion Infection by Thymidine Kinase-Negative Mutants of Herpes Simplex Virus

Tenser, Richard B.; Miller, Richard L.; Rapp, Fred

doi:10.1126/science.224454

Cited by 180 publications

(113 citation statements)

References 8 publications

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“…That is to say that peripheral replication of HSV may induce a non-permissive environment for viral replication in neurons innervating the site of replication. Animal models using corneal infections, have demonstrated that infectious HSV is not detected within trigeminal ganglia until 48 ± 72 h post-infection (Coen et al, 1989;Jenkins and Martin, 1990;Tenser and Edris, 1987). This delay would allow for the establishment of a IL-1/NGF/Oct-2-mediated non-permissive environment.…”

Section: A Viral Vector For Gene Therapymentioning

confidence: 99%

The roles of herpes simplex virus in neuroscience

Turner¹,

Jenkins²

1997

J Neurovirol

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Herpes simplex virus (HSV) has been a focus of research in many laboratories during the last 30 ± 35 years, with the majority centered on the virus' replication, molecular biology and pathogenesis. Recently, HSV has begun to receive considerable attention in the field of neuroscience, where scientists have begun to use the virus as a tool or model for several areas of investigation. These areas include the construction and development of HSV-based vectors for gene therapy and the use of HSV as a neuronal tracer, as a model for demyelinating disease and to study interactions between the nervous, immune and endocrine systems. The goal of this paper is to review these different roles for HSV in the broad field of neuroscience.

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Section: A Viral Vector For Gene Therapymentioning

confidence: 99%

The roles of herpes simplex virus in neuroscience

Turner¹,

Jenkins²

1997

J Neurovirol

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“…More recent studies using genetically engineered TK-deletion mutants have shown that an HSV-2 mutant cannot establish either acute or latent ganglionic infection in mice (McDermott et al, 1984;Tenser & Edris, 1987). Similarly, an HSV-1 mutant was shown to be latency-negative in mice but to establish latent infection in at least a proportion of infected rabbits, suggesting that the host may also be a determinant in the establishment of latent infection (Meignier et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

The Role of Herpes Simplex Virus Type 1 Thymidine Kinase in Pathogenesis

Efstathiou

Kemp

Darby

et al. 1989

Journal of General Virology

218

162

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SUMMARYA genetically engineered herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) deletion mutant has been constructed and used to investigate the role of this gene in pathogenesis. Inoculation of mice with the HSV TK deletion mutant resulted in the establishment of latent ganglionic infection as demonstrated by superinfection of explanted ganglia with wild-type (wt) virus bat not by routine explant culture suggesting that the virus-encoded TK is not essential for the establishment of latent infection but may be necessary for either reactivation or virus replication following reactivation. In addition, Southern blot hybridization has been used to demonstrate in vivo complementation of this mutant by wt virus in both peripheral and central nervous system tissues of mice during acute infection and to show that such complementation can result in the establishment and reactivation of latent TK-infection.

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“…Since the dPK is not essential for virus replication in tissue culture, this conservation suggests that the VZV dPK gene may be important in aspects of infection in vivo. Studies of animal models of HSV infection suggest that the HSV TK may be involved in neurovirulence and also may be important in the establishment of latency (Field, 1982;Price & Khan, 1981;Tenser & Dunstan, 1979;Tenser & Edris, 1987;Tenser et al, , 1981. The high level of VZV dPK conservation also facilitated the recognition of mutations that were likely to be responsible for the loss of dPK activity in the acyclovir-resistant strains studied, since there were single changes between wt parents and drugresistant mutants derived from them.…”

mentioning

confidence: 99%

Molecular Analysis of the Pyrimidine Deoxyribonucleoside Kinase Gene of Wild-type and Acyclovir-resistant Strains of Varicella-Zoster Virus

Sawyer

Inchauspé

Biron

et al. 1988

Journal of General Virology

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SUMMARYThe pyrimidine deoxyribonucleoside kinase (dPK) genes from five wild-type and four acyclovir-resistant varicella-zoster virus (VZV) strains were studied. One of the acyclovir-resistant strains was isolated from a patient receiving chronic acyclovir therapy. Acyclovir-resistant strains expressed the 1.8 kb VZV dPK transcript but lacked dPK activity. To determine the basis for the lack of enzyme activity the dPK gene from each strain was cloned and its DNA sequence determined. The VZV dPK gene was found to be highly conserved among strains, with greater than 99 % nucleotide and amino acid homology. Each acyclovir-resistant VZV strain differed from its wildtype parent in only a single amino acid. The dPK genes from the acyclovir-resistant strains contained either point mutations near the putative thymidine-binding site of the enzyme or ones that resulted in the premature termination of protein synthesis. Single point mutations were sufficient to render these strains dPK-negative and highly resistant to acyclovir. The molecular basis for acyclovir resistance at the dPK locus of VZV is similar to that previously noted to render herpes simplex viruses resistant to acyclovir.

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Trigeminal Ganglion Infection by Thymidine Kinase-Negative Mutants of Herpes Simplex Virus

Cited by 180 publications

References 8 publications

The roles of herpes simplex virus in neuroscience

The roles of herpes simplex virus in neuroscience

The Role of Herpes Simplex Virus Type 1 Thymidine Kinase in Pathogenesis

Molecular Analysis of the Pyrimidine Deoxyribonucleoside Kinase Gene of Wild-type and Acyclovir-resistant Strains of Varicella-Zoster Virus

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