Mechanism of recovery from acute virus infection. VI. Replication of lymphocytic choriomeningitis virus in and clearance from the foot of the mouse.

Abstract

The hind foot was chosen for study of the mechanism by which adult mice clear lymphocytic choriomeningitis (LCM) virus. The T cell-mediated swelling that follows the local inoculation of virus allows parallel investigation of the infectious process and delayed-type hypersensitivity in one organ. A dose of 10(5) mouse infectious units (IU) was optimal, and in all mouse strains tested foot swelling commenced 6 days after injection, with maximal response on days 7 and 8. When mice were sensitized by intravenous (i.v.) infection and challenged locally with infectious virus, the extent of swelling depended on both doses of virus and was most extensive when the interval between primary inoculation and local elicitation was 10 days. The rates of replication of the virus and its clearance were similar in the feet of mice of four strains tested, varying with regard to LCM virus-specific cell-mediated immunity. In CBA/J mice, virus elimination from the foot was followed for a longer time period and was incomplete up to 100 days after infection. A protocol for determining adoptive immunization was established; local inoculation of 10(5) IU was followed 22 h later by i.v. infusion of 1 x 10(8) unselected or 4 x 10(7) T cell-enriched cells from the spleens of syngeneic donors that had been infected i.v. 7 or 8 days previously with 10(3) IU. The concentrations of virus in the recipients' feet began to decline 2 to 3 days thereafter. Adoptive immunization by local inoculation of immune spleen cells was less successful, apparently because the virus multiplied in transferred cells.