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Biomedical subjects

H J Field

Publications and source records attributed to H J Field.

106 records · Page 6Linked to original sources
PubMed1980

Cell-mediated immunity in herpes simplex virus-infected mice: induction, characterization and antiviral effects of delayed type hypersensitivity.

Delayed type hypersensitivity (DTH) was induced ihe reaction was observed 4 to 5 days p.i. and could still be induced up to 18 months later. In contrast, the adoptive transfer of DTH using draining lymph node cells was only possible during the period 6 to 10 days p.i. The cells taken at these times also contained mediators of antiviral immunity, as determined by a marked reduction of virus titres in the ears of infected animals 1 to 3 days after transfer. Draining lymph node cells taken at later times contained mediators of virus immunity, but titres were not reduced until day 5 after the transfer. The cell type involved in both the DTH and antiviral activity was a T lymphocyte, although the particular T cell subsets involved have yet to be determined.

Animals↗
PubMed1980

Sensitivity of viruses to phosphorylated 9-(2-hydroxyethoxymethyl)guanine revealed in TK-transformed cells.

Vaccinia and pseudorabies viruses are resistant to ACV [Acyclovir or 9-(2-hydroxyethoxymethyl)guanine] in normal cells. However, both viruses are sensitive in thymidine kinase (TK)-transformed cells in which the resident HSV-specific TK is able to phosphorylate the drug. This demonstrates the sensitivity of these viruses to phosphorylated ACV and suggests a wider antiviral activity for the phosphorylated drug.

Acyclovir↗
PubMed1980

Isolation and characterization of acyclovir-resistant mutants of herpes simplex virus.

Mutants of HSV which are resistant to acyclovir (acycloguanosine) have been isolated following serial passages of several herpes simplex virus (HSV) strains in the presence of the drug. The majority of the mutants isolated are defective in induction of thymidine kinase (TK) and this is consistent with the observation that independently isolated TK- viruses are naturally resistant to ACV. One mutant is described (SC16 R9C2) which is resistant in biochemically transformed cells which express HSV TK. This suggests that its resistance resides at a level other than TK. It is also resistant to phosphonoacetic acid, suggesting that the DNA polymerase locus may be involved. A further mutant is described [Cl (101) P2C5] which induces normal levels of TK, although the nature of resistance of this virus is not yet elucidated.

Acyclovir↗
PubMed1980

Pathogenicity in mice of strains of herpes simplex virus which are resistant to acyclovir in vitro and in vivo.

Mice infected with three different isolates of herpes simplex virus (HSV) and treated with acyclovir (acycloguanosine; ACV) showed low levels of virus replication during the acute phase of infection. However, virus isolated from such treated mice did not show increased resistance to ACV. In contrast, resistant virus was readily isolated in vitro by passaging HSV in the presence of the drug. The degree of resistance was determined, in part, by the nature of the cells used to test the virus. The majority of ACV-resistant strains induced low or undetectable levels of HSV-specified thymidine kinase (TK), the enzyme responsible for phosphorylating ACV in infected cells. The TK-resistant strains were attenuated when injected into mice as indicated by reductions in virus replication, inflammation, and establishment of latent infections in sensory ganglia. The reduced virulence of the TK- strains was most marked after intracerebral inoculation, where the lethal dose was increased more than 100-fold compared with the parental isolates. However, one mutant is described which induced high levels of TK but was highly resistant to ACV and retained virulence for mice.

Acyclovir↗
PubMed1979

Effect of acycloguanosine treatment of acute and latent herpes simplex infections in mice.

Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form.

Animals↗
PubMed1978

The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice.

The pathogenicity for mice of two mutants of herpes simplex virus (type 1 and type 2), which fail to induce thymidine kinase, were compared with their respective parent strains. The mutants were much less virulent than the parents following either intracerebral or peripheral inoculation. The replication of the virus at the site of inoculation and its progression into the nervous system were studied. Following a very large inoculum in the ear, the type 1 mutant was found to establish a latent infection in the cervical dorsal root ganglia. Mice inoculated intracerebrally with small doses of the mutant viruses were solidly immune to challenge with lethal doses of the parent strain.

Animals↗
PubMed1976

Reactivation of herpes simplex virus infection by ultraviolet light and possible involvement of prostaglandins.

Herpes simplex infection in the mouse ear was used to investigate whether various treatments would reactivate the disease. Immunosuppressive drugs failed to induce clinical signs of reactivation but irradiation of the skin of the originally infected ear with ultraviolet light or injection of prostaglandin E2 or PBSA into this site, caused reactivation of infection. This was detected by the appearance of infectious virus in the skin 2 to 3 days after these treatments. The results are discussed in relation to the mechanism of herpes reactivation in man.

Animals↗
PubMed1975

The pathogenesis of pseudorabies in mice: virus replication at the inoculation site and axonal uptake.

Three-week-old mice were inoculated in the right ear pinna with pseuforabies virus. Ears were surgically removed at various times after inoculation and changes from the normal pathogenesis were observed. Virus replication in the ear tissue and cervical dorsal root ganglia was also monitored. Followed inoculation with a small dose of virus, local multiplication of the virus was necessary before the infection spread to the nerves. With larger infecting doses there was probably direct uptake of virus from the inoculum into the nerve endings. After these larger doses virus was first detected in the dorsal root ganglia 17 h agter infection, suggesting a retrograde axonal flow rate of at lease 1-7 mm/h.

Animals↗
PubMed1975

Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease.

Nineteen recent isolated and three laboratory strains of herpes simplex virus types 1 and 2 were tested for their ability to produce clinical signs in mice following intradermal inoculation in the ear. All viruses produced erythema at the inoculation site; this was the most sensitive clinical sign of infection. Virus multiplication in the ear tissue was similar for both types 1 and 2 up to the fifth day after inoculation but type 2 viruses persisted for longer. Latent infection was demonstrated in cervical dorsal root ganglia. Type 1 viruses required a much higher dose than type 2 to produce neurological signs and death after intradermal inoculation but the difference was less after intracerebral inoculation. Erythema of the inoculated ear recurred sporadically during several months observation in about half the mice that survived intradermal infection with a selected type 1 isolate. The presence of virus in the ear tissue during such recurrences was confirmed by electron microscopy and isolation of infectious virus. The system of ear infection in the mouse is presented as a new model for studying neurovirulence, and latent and recurrent infection with herpes simplex virus.

Animals↗
PubMedDate not supplied

Early therapy with valaciclovir or famciclovir reduces but does not abrogate herpes simplex virus neuronal latency.

Mice were infected via the ear pinna using a recombinant strain of HSV-1 expressing the beta-gal gene under the LAT promoter. Mice were treated continuously with valaciclovir or famciclovir, from 1 day before or 1 day after virus inoculation for 10 days. Ipsilateral and contralateral trigeminal and cervical ganglia were later assessed by co-cultivation or for X-Gal-positive or LAT-positive neurons. Latency was markedly reduced by early therapy, however, a basal level of HSV-1-positive neurons was detected in all mice.

2-Aminopurine↗
PubMedDate not supplied

The development of retinitis in mice with nonfatal herpes simplex encephalitis.

A mutant strain of herpes simplex virus, type 1 (HSV1), selected for high resistance to acyclovir (ACV) was inoculated intracerebrally into mice. The mice survived with no obvious neurological signs but developed cataracts within 4-8 weeks of inoculation. Histological examination revealed only a mild encephalitis, but around 7 days after injection a florid, necrotizing, viral retinitis developed. There was almost simultaneous involvement of both eyes. Inflammatory cell infiltration and early myelin degeneration along the course of the optic nerve suggested cell to cell spread of virus to the retinal nerve cell bodies. Although virus could only be recovered from the eye in the early stages of retinitis, destruction of the neural retina was frequently complete and subsequently the optic nerve showed Wallerian type degeneration. Visible cataracts were a late complication, but changes in the lens were initiated during the phase of acute retinitis. This experiment shows that antiviral agents may induce mutant forms which cannot reproduce classical disease, but are capable of permissive infection in unexpected sites. Herpes retinitis is occasionally recognized as a complication of fatal HSV encephalitis in man. Theoretically, more effective treatment of encephalitis with nucleoside analogues, for example with acyclovir, could reveal the development of retinitis in survivors.

Animals↗