The cellular nature of genetic susceptibility to a virus.

Using peritoneal macrophage cultures it was found that both PRI mice and their macrophages in culture were susceptible to mouse hepatitis virus and that C(3)H mice and macrophages were resistant. All F(1) macrophages and some back-cross cell cultures were susceptible. The degeneration of F(1) and back-cross macrophages obtained either from adult mouse peritoneal exudate or newborn mouse liver, occurred more slowly than PRI macrophages. Segregation of susceptibility occurred in the first back-cross generation. Tests of three back-cross generations from susceptible mice yielded about one-quarter of the mice shown to be susceptible either by direct test or test of their macrophages. A clear correlation between susceptibility in vivo and in vitro was established both in the test of the percentage segregation and in tests of individual back-cross mice. A small series of tests, however, indicated that 50 per cent of the back-cross mice had the genetic capacity to transmit susceptibility. Thus a hypothesis of two genes for susceptibility, although not excluded, may yield to a hypothesis of a single dominant gene, incompletely expressed. Resistant cells were converted into susceptible cells by ingestion of a relatively large particle containing a heat-stable substance. This susceptibility, although complete, was temporary. The nature of the factor causing the change has been discussed.