Search

The role of spreading somatic cell infections with ecotropic MuLV viruses in the induction of plasmacytomas in BALB/cAN pi mice was determined by constructing congenic mice that lacked the gene locus Cv that codes for ecotropic virus. DBA/2 mice that lack Cv on chromosome (chr) 5 carry a closely linked gene Rmcfr that determines resistance to infection with mink cell focus-forming viruses (MCF). Rmcfr was retrogressively back-crossed onto BALB/c for six successive generations to produce N6 mice. N6 mice were mated to each other to produce BALB/c.DBA/2 Rmvfr/Rmcfr homozygotes. This stock of mice lacked Cv, as demonstrated by DNA hybridization and were as fully susceptible to developing plasmacytomas as the parental BALB/c. A second congenic stock BALB/c.DBA/2 Rmcfr/Rmcfr Fv-1n/Fv-1n was also developed, but the mice of this stock showed a reduced incidence of plasmacytomas, as did BALB/c.DBA/2 Fv-1n/Fv-1n mice. These findings indicated Fv-1 or a gene closely linked to it conferred partial resistance to plasmacytomagenesis. In constructing the BALB/c.DBA/2 Fv-1n/Fv-1n stock, a "control" congenic BALB/c.DBA/2 Fv-1b/Fv-1b was also developed at N6. Surprisingly, this stock carried the Qa2+ trait. These mice were also partially resistant to plasmacytomagenesis, suggesting a gene on chromosome 17 (the location of Qa2) or a gene located elsewhere that regulates Qa2 expression is linked to a gene controlling partial resistance to plasmacytoma development.

The resistance to N- and B-tropic viruses controlled by the murine genetic locus Fv-1 was studied by dose-response analyses, using infectious center plating onto sensitive cells to determine the number of virus-producing cells. Three components contributing to the reduced plaquing efficiency on Fv-1 resistant cells were identified. First, the dose-response relations in Fv-1 resistant cells showed multiple-hit kinetics; most virus strains showed 2-hit kinetics, but the Gross Passage A virus gave 3-hit kinetics. This hitness factor is considered to represent the basic effect of Fv-1. Second, in many instances only a small fraction of Fv-1 resistant cells receiving the minimum required number of hits actually became virus producers. Third, only a fraction of the virus-producing cells registered as plaques when left in situ with resistant cells, due to the relative inefficiency of subsequent cycles of infection. Strain DBA/2 cells differed from those of other Fv-1n strains in showing only the hitness component. Fv-1nb hybrid cells showed multiple-hit dose-response curves with both N- and B-tropic viruses. Once infection has been established, virus yield from sensitive and resistant cells is similar.

Quantitative studies were made of the organ distribution of murine leukemia virus in AKR mice of various ages. Infectious virus first appeared shortly before or after birth and was continuously present in all mice thereafter. Highest infectivity titers were found in uterus and bone, with spleen slightly lower. Virus titers in normal thymus were relatively low, but increased significantly with the development of thymic lymphoma. The level of viremia decreased after the 1st month of life, but increased sharply in lymphomatous mice.