ABSTRACT
The influence of the T-lymphocyte-stimulating dipeptide bestatin on the induction of neutralizing antibodies against herpes simplex virus type 1 in the mouse was investigated. Dose-response experiments revealed two active ranges from 1 ng/kg to 100 ng/kg and from 10 micrograms/kg to 10 mg/kg or more. Bestatin (10 mg/kg) enhanced antibody levels after primary infection, if injected between day 5 and day 8 after infection with a maximum effect at day 5. Following secondary infections, bestatin was most effective at day 1 after secondary infection. Moreover, the antibody-generating potency of a formalinized herpes simplex virus type 1 vaccine was elevated considerably. Bestatin and silica seemed to be effective systemically. Treatment of mice with silica before virus infection and additionally with bestatin at day 1 after infection resulted in an additive effect on antibody production. Comparable effects could be obtained when polyinosinic acid X polycytidylic acid or indomethacin was combined with bestatin at day 1. It was assumed that certain factors released by macrophages 'sensitize' the antibody-producing system for the enhancing activity of bestatin at day 1. Indeed, culture fluids of macrophages obtained from mice either pretreated with silica or infected by herpes simplex virus were active in enhancing antibody formation upon injection into mice at day 1 in combination with bestatin. Bestatin did not induce interferon activity. No influence of bestatin on the virus content of organs or on mortality was observed.
Subject(s)
Antibody Formation/drug effects , Leucine/analogs & derivatives , Simplexvirus/immunology , Animals , Chlorocebus aethiops , Female , Hemolysin Proteins/analysis , Indomethacin/pharmacology , Interferons/analysis , Leucine/administration & dosage , Leucine/pharmacology , Male , Mice , Mice, Inbred C57BL , Poly I-C/pharmacology , Rabbits , Silicon Dioxide , Time FactorsABSTRACT
The in vitro replication of eleven different strains of herpes simplex virus type 1 was studied in resident or thioglycollate-stimulated mouse macrophages. The strains of herpes simplex virus differed in the type of cytopathic effect, induction capacity for herpes simplex virus coded thymidine kinase and pathogenicity in the mouse. Herpes simplex virus replicated better in thioglycollate-stimulated macrophages than in resident macrophages. In vitro ageing of macrophages increased their replicative potency. Herpes simplex virus replicated better in macrophages from homozygous bg/bg C57/BL6J mice than in macrophages from their heterozygous littermates. Separation of macrophages on discontinuous Percoll-gradients revealed 4 fractions with identical potency for replication. The ability of herpesvirus to replicate in macrophages varied from strain to strain of virus i.e. Wal greater than Len, clone 4 of Len, greater than L3-2s, JES, Ang-, Ang + path, clone 2 of Len and greater than MDK clones. The ability to cause cytopathology also varied. Only strains Ang- and Ang + path showed limited or late cytopathology in macrophages. The cell-fusing property of herpes simplex virus appeared to be more closely correlated with lower replication rates than production cell rounding. Thymidine kinase- viruses replicated less well than thymidine kinase+ or thymidine kinase(+) strains. Strains of herpes simplex virus with high or low pathogenicity for mice replicated in macrophages to the same degree. The phagocytic activity of macrophages for IgM-coated sheep red blood cells was inhibited earlier by strains of herpes simplex virus of type 2 than by strains of herpes simplex virus of type 1.
Subject(s)
Macrophages/microbiology , Simplexvirus/physiology , Animals , Ascitic Fluid , Cells, Cultured , Cytopathogenic Effect, Viral , Enzyme Induction , Erythrocytes , Macrophage Activation , Macrophages/immunology , Mice , Mice, Inbred C57BL , Mice, Inbred Strains , Phagocytosis , Simplexvirus/enzymology , Simplexvirus/pathogenicity , Thymidine Kinase/biosynthesis , Virus ReplicationABSTRACT
The kinetics of antibody synthesis was investigated after intraperitoneal, subcutaneous, and footpad infection of various strains of mice with herpes simplex virus. Immunoglobulin M antibodies appeared 5 days after and immunoglobulin G antibodies appeared 10 to 12 days after intraperitoneal infection with herpes simplex virus type 1. The major histocompatibility complex and the background genome of inbred mice were not found to have a systematical influence on antibody synthesis. Female mice, however, consistently produced more antibodies than did male if the infection was done intraperitoneally, but not if it was done subcutaneously or into footpads. Castration considerably increased the amount of antibodies produced by male mice. The difference in antibody formation between females and males could be abolished by injection of silica; moreover, antibody titers were enhanced by this treatment. This has also been found by immunization with a Formalin-inactivated herpes simplex virus vaccine. The effect of silica in enhancing antibody formation could be observed up to 12 days after infection. Infectious virus could be detected up to 2 days after infection, and herpes simplex virus type 1 antibody-stimulating antigens could be detected up to 4 days in ultrasonicates of macrophages. The assumption is made that androgen-sensitive cell populations, including macrophages and their soluble products, are involved in antibody-depressing mechanisms.
