Abstract
The pathogenicity pattern of the HSV-1 strain ANG which is nonencephalitogenic in mice is compared with that of a selected neurovirulent variant of this strain in DBA-2 mice. After i.p. inoculation both variants replicate to high titers in the mouse peritoneum and build up a virus reservoir in the spleen. Both viruses have no effect on visceral mouse organs other than the spleen; both viruses lead to an inefficient and masked viraemia and both replicate efficiently in CNS tissue after direct intracranial injection. Only the pathogenic variant, however, spreads to the CNS and leads to lethal encephalitis upon intraperitoneal infection. The assumption that infection of the CNS would be mediated by hematogenous transport is not supported by the data obtained from transfer and cocultivation experiments with lymphocytes or experiments involving artificial viraemia. In a model to analyse the capacity of the viruses to invade nerve axons and to induce a latent infection both viruses were found to be latency positive in dorsal root ganglia. It is clear that non-neurovirulent HSV-1 strains are subjected to a postganglionic block of virus spread from the periphery to the CNS. The experiments led to the hypothesis that axonal transport even beyond the dorsal root ganglia to the CNS proceeds unrestricted, whereas lethal CNS invasion is prevented by a restriction of viral replication of HSV-1 ANG in the CNS by a virus-induced host defence mechanism.
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Caspary L, Schindling B, Dundarov S, Falke D (1980) Infections of susceptible and resistant mouse strains with herpes simplex virus type 1 and 2. Arch Virol 65:219–227
Cook ML, Stevens JG (1973) Pathogenesis of herpetic neuritis and ganglionitis in mice: evidence for intraaxonal transport of infection. Infect Immun 7:272–288
Darai G, Munk K (1976) Neoplastic transformation of rat embryo cells with herpes simplex virus. Int J Cancer 18:469–481
Dix RD, McKendall RR, Baringer JR (1983) Comparative neurovirulence of herpes simplex virus tyoe 1 strains after peripheral or intracerebral inoculation of Balb/c mice. Infect Immun 40:103–112
Field HJ, Wildy P (1978) The pathogenicity of thymidine kinase-deficient mutants of herpes simplex virus in mice. J Hyg (Camb) 81:267–277
Hill TJ, Field HJ, Blyth WA (1975) Acute and recurrent infection with herpes simplex virus in the mouse: a model for studying latency and recurrent disease. J Gen Virol 28:341–353
Honess RW, Watson DH (1977) Unity and diversity in the herpes viruses. J Gen Virol 37:15–37
Kaerner HC, Ott-Hartmann A, Schatten R, Schröder CH, Gray CP (1981) Amplification of a short nucleotide sequence in the repeat units of defective herpes simplex virus type 1 Angelotti DNA. J Virol 39:75–81
Kaerner HC, Schröder CH, Ott-Hartmann A, Kümel G, Kirchner H (1983) Genetic variability of herpes simplex virus: I. Development of a pathogenic variant during passaging of a nonpathogenic HSV-1 virus strain in mouse brain. J Virol 46:83–93
Kirchner H (1982) Immunobiology of infection with herpes simplex virus. In: Melnick JL (ed): Monographs in Virology 13. Karger Verlag, Basel, pp. 1–104
Kümel G, Hennes-Stegmann B, Schröder CH (1981) Interference in HSV-1 ANG: Methylation pattern and ribonucleotide content of viral DNA. In: Kaplan AS, LaPlace M, Rapp R, Roizman B (eds): International Workshop on Herpes Viruses. Esculapio Publ Co, Bologna, Italy, pp. 24–25
Kümel G, Hennes-Stegmann B, Schröder CH, Knopf KW, Kaerner HC (1982) Viral interference of HSV-1: Properties of the intracellular viral progeny DNA. Virology 120:205–214
Kümel G, Kirchner H, Zawatzky R, Engler H, Schröder CH, Kaerner HC (1982) Experimental infection of inbred mice with herpes simplex virus. V. Investigations with a virus strain non-lethal after peripheral infection. J Gen Virol 63:315–323
Lonsdale DM, Brown SM, Lang J, Subak-Sharpe JH, Koprowski H, Warren KG (1980) Variations in herpes simplex virus from human ganglia and a study of clonal variation in HSV-1. Annals of the New York Academy of Science: 219–308
McKendall RR, Klassen T, Baringer JR (1979) Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread. Infect Immun 23:305–311
Renis HE, Eidson EE, Mathews J, Gray JE (1976) Pathogenesis of herpes simplex virus types 1 and 2 in mice after various routes of inoculation. Infect Immun 14:571–578
Richards JT, Kern ER, Overall JC Jr, Glasgow LA (1981) Differences in neurovirulence among isolates of herpes simplex virus types 1 and 2 in mice using four routes of infection. J Infect Dis 144:464–471
Russel WC (1962) A sensitive and precise plaque assay for herpes virus. Nature 195:1028–1029
Schneweis KE, Forstbauer H, Olbrich M, Tag M (1984) Pathogneesis of geneital herpes simplex virus infection in mice. III. Comparison of the virulence of wild and mutant strains. Med Microbiol Immunol 173:187–196
Schneweis KE, Gruber J, Hilfenhaus J, Möslein A, Kayser M, Wolff MH (1981) The influence of different modes of immunization on the experimental genital herpes simplex viurs infection of mice. Med Microbiol Immunol 169:269–280
Schröder CH, Stegmann B, Lauppe HF, Kaerner HC (1975/76) An unusual defective genotype derived from herpes simplex virus ANG. Intervirology 5:173–184
Schröder CH, Engler H, Kirchner H (1981) Protection of mice by an apathogenic strain of HSV-1 against lethal infection by a pathogenic strain. J Gen Virol 52:159–161
Schröder CH, Kümel G, Glorioso J, Kirchner H, Kaerner HC (1983) Neuropathogenicity of herpes simplex virus in mice: Protection against lethal encephalitis by coinfection with a nonencephalitogenic strain. J Gen Virol 64:1973–1982
Wagner MJ, Summers WC (1978) Structure of the joint regions and the termini of the DNA of herpes simplex virus type 1. J Virol 27:374–387
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Kümel, G., Schröder, C.H. & Kaerner, H.C. Neurovirulence and latency in inbred mice of two HSV-1 intrastrain variants of divergent pathogenicity. Med Microbiol Immunol 174, 313–324 (1986). https://doi.org/10.1007/BF02123684
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DOI: https://doi.org/10.1007/BF02123684