In some apparently healthy mice the virus of lymphocytic choriomeningitis persisted for a considerable period of time after recovery, in the blood, urine, and nasal secretions, while in other mice it soon became undemonstrable. It is possible that the persistence of the virus is due to lesions in the lungs, liver, and kidneys. The immunity to lymphocytic choriomeningitis in mice does not seem to depend upon the presence of virus in the blood and the organs tested. No antivirus was detected in sera from several solidly immune mice, which fact suggests that circulating antivirus plays no important part in their immunity. Leucocytes also seem to be no essential factor in this immunity, which probably is closely linked with the tissues. The urine of guinea pigs which had recovered from severe attacks of lymphocytic choriomeningitis contained virus for a few weeks after recovery, while that from mild cases contained no virus. Virus was never demonstrated in the blood of immune guinea pigs. Antivirus was readily detected in it.

In a mouse colony in which lymphocytic choriomeningitis is endemic infection takes place either in utero or shortly after birth. Virus is discharged from infected mice with the nasal secretions and urine. In some mice the infection lasts for several months, and such carriers can transmit the disease to healthy mice by contact. The portal of entry appears to be the nasal mucosa rather than the gastrointestinal tract. Mice infected by contact show no definite symptoms while those infected in utero often do. The disease has persisted in the colony for at least 15 months without change in its character. Mouse stocks differ in their susceptibility to contact infection and the findings given in the paper could be reproduced only with a very susceptible stock. Wild mice (Mus musculus) can be infected by contact, although less easily than our white mice. The source of the infection in the colony has not been determined. The fact that the serum of the caretaker neutralizes the virus indicates that he has been infected. It seems likely that the virus went from him to the mice rather than vice versa. Other possible sources of infection are considered.

Mice infected in utero continued to carry choriomeningitis virus in the blood more regularly and in greater amount than suckling mice infected by contact. This result may be due to the difference in tissue maturity at the time of infection: the more immature the tissues are when infected, the longer the virus appears to persist in them after maturation. A similar result was obtained with mice of different ages infected either by contact or by intranasal instillation of virus, in that the carrier state lasted longer in the younger animals. This cannot be attributed entirely to the difference in age, however, since young mice as a rule showed more severe symptoms than mature animals. It is possible, therefore, that the difference in the severity of the disease accounted in part for that in the duration of the infection. In mature mice infected experimentally as well as in some of the suckling mice infected by contact the severity of the disease was the determining factor, the infection persisting longest in those animals that showed the most severe reaction. The character of the virus used also appeared to influence the persistence of the virus in the blood. A strain of virus isolated in 1935 from an infected stock mouse and modified by intracerebral passage in mice (5) disappeared from the circulation more rapidly than the stock strain maintained by natural passage in the infected mouse stock. The guinea pig passage strain, however, which was obtained from the same mouse as the mouse passage virus but passed through guinea pigs by pad inoculation, persisted in the blood more frequently than the stock strain. Carrier mice without exception had a high degree of immunity to intracerebral injection with virus, while other animals once infected but no longer carrying detectable amounts of virus in the blood often showed an incomplete immunity that manifested itself in an accelerated, non-fatal reaction, presumably of an allergic nature. This observation does not prove, however, that the immunity always is an "infection immunity," since a high degree of resistance not associated with detectable amounts of virus in the blood and brain was produced by repeated injections with the mouse passage strain. Since the blood and the tissues of old carriers often contain large amounts of virus, it is very unlikely that their immunity is due to protective antibodies circulating in the blood or fixed in the tissue spaces. It rather appears that the susceptible cells of such animals are infected and that cells occupied by actively multiplying virus cannot be reinfected. The mechanism of this infection immunity as well as the immunity apparently not associated with infection requires further study.

No abstract

A small mouse stock in which lymphocytic choriomeningitis is endemic has been observed over a period of 4 years. The disease has persisted during that time, but it has become so mild that it can no longer be recognized by clinical observation. In spite of this fact, all of the stock mice tested, both young and old, carried considerable amounts of virus in their organs and blood. The females readily transmit the infection to their offspring. Intrauterine infection has become the only mode of transmission of the disease in contrast to the situation in 1935 when a certain number of mice were born virus-free and became infected by contact shortly after birth. The present mildness of the disease appears to be due to two factors, namely, the change in its mode of transmission just mentioned, and a shift in the severity of the disease with regard to the age of the host at the time of infection. This shift has occurred gradually since 1935 when the mice infected in utero were the only ones to become sick. Since 1937, however, the virus is quite harmless for such animals and produces symptoms only in suckling mice from the virus-free stock exposed to contact infection. Evidence is presented which suggests that the shift in the severity of the disease was caused by a decrease of the pathogenicity of the virus for embryonic mouse tissue and a concurrent increase of the resistance to intrauterine infection of the mice from the infected stock. Another change noted concerned the communicability of the experimental disease. In contrast to observations made in 1935 the experimental infection of mature mice from the virus-free colony is now very rarely transmitted by contact to healthy mice, young or old. Suckling mice from the same stock infected by intranasal instillation of virus, however, readily transmit the disease and continue to do so as they grow up. The same is true for mice infected naturally. The reason for this discrepancy has not been ascertained, but it has been shown that naturally infected mice capable of transmitting the disease in general discharge large amounts of virus through the nose for a longer period of time than mature mice infected experimentally which fail to transmit their infection. It may likewise be of significance in this connection that the virus can lose its communicability by animal passage. A marked change (chiefly climatic and dietary) in the environmental conditions of the infected stock failed to influence the course and character of the epidemic.