Variation in Virulence for Mice and Rhesus Monkeys Among St. Louis Encephalitis Virus Strains of Different Origin

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Abstract
The virulence characteristics of 67 strains of St. Louis encephalitis (SLE) virus isolated from various sources in North, Middle, and South America were compared in mice and rhesus monkeys. Each virus strain was titrated in mice exactly 21 days old and virulence was expressed as the ratio of intracerebral (ic)/intraperitoneal (ip) LD50. Virus strains fell into three groups: 1) high virulence (ic/ip LD50 ratio ∼1.0); 2) intermediate virulence (variable mortality over a wide dose range); and 3) low virulence (ic/ip LD50 ≤ 0.00002). Virus strains isolated during Culex pipiens and Cx. nigripalpus-borne epidemics in the eastern United States were highly virulent for mice, whereas a high proportion of the endemic virus strains isolated from Cx. tarsalis in the western United States were attenuated. Virus strains isolated from birds (the usual host for SLE virus) were highly virulent, in contrast to strains from rodents and carnivores, which were attenuated. Isolates from humans exhibited variable virulence characteristics. In experimentally-infected mice, virulence correlated with high viremia, replication in extraneural tissues, and earlier neuroinvasion. Mouse virulence correlated with clinical and histopathologic markers of pathogenicity for ic inoculated rhesus monkeys. Monkeys immunized with nonpathogenic strains by subcutaneous inoculation were partially protected against ic challenge with a virulent virus strain. The virulence classification of SLE virus strains is discussed in terms of epidemiologic correlations. This classification provides a framework for future studies on the antigenic, genetic, and biochemical bases for SLE virus strain variation.