The spread of HSV of type 1 and 2 was investigated after intraperitoneal, intraplantar and intracerebral infections of resistant (C57/bl) and susceptible (NMRI) mice. The virus spreads after i.p. infection to the spleen and the liver to the same extent in both strains of mice. However, virus is eliminated earlier in resistant mice. Intracerebral infections revealed a peculiar type of resistance of C57/bl mice especially for type 2 of HSV. HSV multiplies in the thymus at the early stage of infection and can be detected in this organ in sick mice of NMRI strain. HSV-1 and 2 can be detected in the spinal cord of C57/bl mice without sickness or death of these animals.
The cytotoxicity and the antivirus activity of native hemocyanin, RtH, derived from the Bulgarian marine mollusk Rapana thomasiana and its structural isoform, RtH2, against HSV replication was evaluated on three HSV strains Ð two wt strains, TM (HSV 1) and Bja (HSV 2), and one ACV R mutant with tk gene mutation, DD (HSV 2). The experiments were performed on continuous RD 64 cells and three HSV 1 and HSV 2 strains were used, two mutants sensitive to acyclovir and one resistant mutant.Both compounds were found to be effective inhibitors of wt HSV replication. Both compounds did not exhibit any effect on the infectious virus yield on ACV R mutant. The most promising, active and selective, anti-HSV agent, especially to genital herpes virus, was found to be the functional unit of native hemocyanin Ð RtH2. RtH2 did not induce apoptosis/ necrosis 8 h after virus infection and the target of its action, was found to be the viral but not the host cell DNA.
Herpes simplex virus strains (HSV) were isolated from various herpetic diseases. These HSV-strains isolated in Bulgaria (687) and in other countries (13) were studied by the neutralization test using standard type specific rabbit antisera and human gamma globulin. The serotype distribution of all strains showed: HSV-1 = 323 strains, HSV-2 = 372 strains, 5 strains behaved antigenically intermediate. A close correlation between the serotype of the strains and the localization of the lesions was established. All but four strains (1.24 per cent) isolated from the head belong to HSV-1, and only six HSV-strains (1.9 per cent) from lesions with other localizations were not HSV-2. Within six months to 8 years 2 to 4 herpes strains were isolated repeatedly from 30 patients. In 23 of these cases they were identical and in the other they showed different biological (3) or antigenical (4) properties. The results suggest, that under natural conditions some HSV-intermediate strains may exist.
The thymidine kinase inducing ability of 104 strains of herpes simplex virus was studied comparatively. A pronounced relationship was established between induction of the enzyme and the serotype of the strains. As a rule, the strains of serotype 2 are weaker inducer of dThd- and dCyd-kinase activity than serotype 1 strains. A certain parallelism exists between induction of both enzymes, however the activity of the thymidine kinase increases after infection with herpes simplex virus 4--5 times more than that of the dCyd-kinase. Adaptation of the strains to cell cultures only slightly modifies the inducing ability of the herpes simplex virus strains. The thymidine kinase activity induced by HSV-1 and HSV-2 differ from each other and are different from the cell enzyme with respect to their thermal stability at 40 degrees C. These differences are expressed more clearly in the presence of 480 muM dThdMP during inactivation. dThdMP stabilizes the type 1 but not the type 2 enzyme.
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