Factors Influencing the Persistence of Choriomeningitis Virus in the Blood of Mice after Clinical Recovery

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.