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Biomedical subjects

B Meignier

Publications and source records attributed to B Meignier.

42 records · Page 3Linked to original sources

Colonization of murine ganglia by a superinfecting strain of herpes simplex virus.

We report on the colonization of murine trigeminal ganglia after sequential infection of mice by herpes simplex viruses (HSVs). In preliminary studies, we have established that whereas the HSV-1(F) strain efficiently colonizes ganglia when inoculated by either the ear or eye routes, the HSV-1 X HSV-2 recombinant C7D colonizes ganglia when inoculated by the eye route only. The experimental design consisted of inoculating the right eye with C7D on day 1 and with HSV-1(F) in both left and right eyes on day 26. Both right and left trigeminal ganglia were removed and analyzed independently for latent virus on day 52. Our studies indicate that HSV-1(F) viruses were recovered from all left trigeminal ganglia but from only a small number of right trigeminal ganglia. Some right trigeminal ganglia yielded no viruses, whereas others yielded both C7D and HSV-1(F) viruses identified on the basis of plaque morphology and restriction enzyme cleavage patterns of viral DNA. The results indicate that more than one virus may colonize the same ganglion and that trigeminal ganglia may be protected from colonization by a superinfecting virus by determinants acting at a local level in the absence of demonstrable virus.

Animals↗

Application of molecular genetics to the design of live herpes simplex virus vaccines.

In principle, several avenues for attenuation of herpes simplex viruses (HSV) are now available. These include intermixing of HSV-1 and HSV-2 genes by recombination, altering the regulation of gene expression and the deletion of viral genes not required for replication of the virus in permissive cells in culture. Results of analyses of HSV-1 x HSV-2 recombinants and of mutants containing a deletion in a gene expressed early in infection showed a loss of virulence when infected by intracerebral route into adult Balb/c mice. In addition, immunization of the mice by intracerebral route with relatively low doses of virus protected the mice from challenge with high doses (3000 LD50) of virulent virus. The application of genetic engineering to the construction of live vaccines is discussed.

Chromosome Deletion↗

Foot and mouth disease virus production on microcarrier-grown cells.

The industrial usefulness of the production of foot and mouth disease virus with microcarrier grown cells has been tested at a large scale. The vaccines, intended for pigs, prepared with such virus give a good level of immunity against virulent challenges. They are stable and free from side effects.

Animals↗

Cell culture on beads used for the industrial production of foot-and-mouth disease virus.

The microcarrier culture technique has been applied to a pig kidney cell line. Microcarriers consisted of DEAE Sephadex A 50 beads washed and containing carboxymethyl cellulose. Sifted beads gave better results than unclassified material. Cells for inoculum were prepared in Roux flasks. The two types of fermentors which were used (operating capacity 100 l and 150 l) gave similar results. The growth of the cells can easily be followed by microscopic observation and cell count. The yields of cells per volume of spent medium were three times higher on microcarrier than in Roux bottles; the average doubling time was not modified. Foot-and-mouth disease virus can be produced with cells grown on beads. Vaccines prepared with these viruses induced good protection for pigs.

Animals↗

Genetically engineered attenuated herpes simplex viruses.

Two recombinant herpes simplex viruses, of type 1 background, were constructed with two large deletions and duplicate sets (type 1 and type 2) of the genes coding for glycoproteins D, G, and E. One recombinant (R7020) is thymidine kinase-positive, and the other (R7017) is thymidine kinase-negative. Evaluation in rodents indicated that these viruses are genetically stable, capable of establishing latency, protective against severe herpetic diseases, and protective against the establishment of latency. In Aotus monkeys, R7020 replicates at the site of inoculation but does not disseminate in the body. It can reactivate from the latent state but without causing recurrent lesions, even in immunosuppressed monkeys.

Animals↗