The Pathogenesis of Lymphocytic Choriomeningitis in Mice: the Effects of Different Inoculation Routes and the Footpad Response

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Abstract
Summary: A detailed study of the different host responses after inoculation of mice with lymphocytic choriomeningitis (LCM) virus by different routes was made using s.c., i.p., i.c. and f.p. inoculations. Mice of two different strains were observed for clinical disease signs, the progress of which was followed objectively by recording the over-all weight changes of the mice for a 2-week period after inoculation; both aggressive and docile virus strains were used. High doses of the docile virus strain given by the i.c. inoculation route did not regularly produce disease and death, particularly in the Swiss mice. This phenomenon was concluded to be due to immunologic paralysis. In this and in some other cases, the immunizing titer of virus preparations was higher than the LD50 titer. Subcutaneous inoculation caused very low mortality with the production of immunity. Footpad inoculation production of immunity. Footpad inoculation produced a severe edematous response which was the most reliable and sensitive clinical method of detecting docile virus strains. The measurements of weight changes in the inoculated mouse proved to be the most sensitive index of disease. By recording weight changes, it is possible to judge the end point of LCM virus titration after approximately 4 days instead of the usual 10 days to 2 weeks. The method also indicates the presence of virus in doses which ordinarily do not cause detectable clinical response. The findings are discussed in terms of the pathogenic mechanism of LCM infection.