Effect of silica on the pathogenic distinction between herpes simplex virus type 1 and 2 hepatitis in mice

Abstract

The role of macrophages in the difference in liver pathogenicity between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in mice was investigated by selectively blocking the macrophage function of the mice by silica. Intravenous administration of 3 mg of silica 2 h before virus inoculation partially abolished the difference between the two virus types, as judged by macroscopic and microscopic examination of the livers and by virus isolation studies. Intraperitoneal inoculation of 50 mg of silica before virus seemed more effective in suppressing the macrophage function, since this treatment almost completely eliminated the difference in hepatotropism between HSV-1 and HSV-2 as assessed by the number and size of the lesions appearing in the liver. The final outcome of the infection, death from encephalitis, was, however, not influenced by macrophage blockade.In a previous study it was shown that a specific pathogenic distinction exists between herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection in mice (11). On intraperitoneal (i.p.) inoculation with strains of HSV-2, most mice develop progressive focal necrotizing hepatitis, whereas HSV-1 only occasionally produces a few tiny self-limiting foci of necrosis in the liver.Recently, the role of macrophages in this difference in pathogenicity between the two closely related virus types was examined, and results were presented which indicated that macrophages might play a crucial part in the phenomenon, as it was shown that the restriction of HSV-1 replication in peritoneal macrophages from mice was much greater than that of HSV-2 replication (10).Silica, an agent reported to be selectively toxic for macrophages (2, 6), has been used in several studies to delineate the role of macrophages in the host defense mechanisms against a variety of virus infections (3-5, 7, 12-16). The purpose of the present study was to add further evidence to the role of macrophages in the pathogenic action of HSV-1 and HSV-2 in mice by selectively blocking the macrophage cell population by administration of silica.MATERIALS AND METHODS Mice. Four-week-old female inbred specific-path ogen-free mice of the BALB/c/A/BOM strain were used. They were obtained from Gl. Bomholtgaard Viruses. HSV strains MacIntyre (HSV-1) and MS (HSV-2), used in this study, were described previously (11). Silica. Silica in the form of Dorentrup Quartz no. 12 (<5 gm) was kindly provided by and has been found active for macrophage blockade in his hands (J. Lindenmann, personal communication). Dry, autoclaved silica was suspended in phosphate-buffered saline just before use at a concentration of 15 mg/ml for intravenous (i.v.) and 50 mg/ml for i.p. injection. Immediately before injection it was dispersed by brief exposure to ultrasonic vibration.In vivo experiments. Silica was injected slowly in the tail vein (3 mg/0.2 ml) of 4-week-old BALB/c mice. Two hours after the silica injection, the mice were inoculated i.p. with 105 plaque-forming units of either HSV-1 or HSV-2 in 0.1 ml of diluent. Groups...

Role of activated macrophages in resistance of congenitally athymic nude mice to hepatitis induced by herpes simplex virus type 2

“…During the course of infection, the development of liver lesions was followed in all groups of mice by histological examination of the livers from each day of the experiment. In BALB/c and nu/+ mice the microscopic development of the lesions was quite comparable to earlier descriptions (20,21), whereas regular lesions were absent in nude mice infected at 6 weeks of age. The livers of nude mice examined at any day of the experiment were further characterized by a general Kupffer cell proliferation.…”

“…Effect of silica on HSV-2 hepatitis in nude mice. In previous studies, silica has been found effective in blocking the macrophage restriction of HSV replication in livers of mice (19,20). Therefore, it was investigated whether the augmented resistance of nude mice could be abolished by silica treatment.…”

“…Macrophage restriction of virus replication has been found important in other aspects of mouse resistance to HSV (14,16,(18)(19)(20). Furthermore, reports on the role of activated macrophages in resistance of nude mice to other pathogens (5,10,29) stimulated an investigation of the handling of HSV-2 by peritoneal macrophages from nude mice.…”

“…Silica pretreatment. A silica suspension of 15 mg/ml was prepared as previously described (20). Mice were inoculated intravenously with 0.2 ml (3 mg/mouse) 2 h before the virus inoculation.…”

Anti‐tumor effects of interferon in mice injected with interferon‐sensitive and interferon‐resistant friend erythroleukemia cells. VIII. Role of the immune system in the inhibition of visceral metastases

“…Silica is toxic for macrophages (Kessel et al, 1963;Allison et al, 1966;Pearsall and Weiser, 1968) and i.v. injection of mice with silica impairs liver macrophage function (Zisman et al, 1971;Mogensen and Andersen, 1977). As can be seen in Table V,…”