Effect of immunosuppression on the genetic resistance of A2G mice to neurovirulent influenza virus.
A2G mice are genetically resistant to lethal infection with neurotropic and pneumotropic influenza viruses. A possible immunological explanation for this resistance was sought by assessing the effect of cyclophosphamide and X irradiation immunosuppression on the infection of A2G mice with lethal doses of neurovirulent virus. Immunosuppressed A2G mice survived lethal infection enen though rendered unable to produce specific antiviral antibody or to generate cell-mediated delayed-type hypersensitivity responses. Measurement of infectious virus replication and detailed observation of the infection by immunofluorescence microscopy show that immunosuppression does not potentiate or allow spread of the virus in A2G brains. Interferon levels were essentially the same in normal and immunosuppressed A2G brains but were 3 to 5 times lower than in the brains of susceptible mice dying of the infection. The results strongly suggest that the genetic resistance of A2G mice to the acute lethal effects of neurovirulent influenza virus infection does not depend on the induction of primary immune mechanisms as we currently understand them. Other possible explanations for this resistance are considered.
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001921:Brain / Q000276:immunology; D046508:Culture Techniques; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D005455:Fluorescent Antibody Technique; D006385:Hemagglutination Inhibition Tests; D006460:Hemolysin Proteins / Q000032:analysis; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007106:Immune Sera; D007109:Immunity; D007114:Immunization; D007165:Immunosuppression Therapy; D007372:Interferons / Q000032:analysis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011817:Rabbits / Q000276:immunology; D011833:Radiation Injuries, Experimental; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D010948:Viral Plaque Assay
D000914:Antibodies, Viral; D006460:Hemolysin Proteins; D007106:Immune Sera; D003520:Cyclophosphamide; D007372:Interferons