Mechanism of restriction of murine leukemia viruses varies between different strains of Fv‐1 n mice

The mechanism of Fv‐1 restriction in DBA/2 ( Fv‐1 n ) mouse cells was investigated by quantitative infectious center assays employing a newly isolated continuous cell line. Titration of B‐tropic murine leukemia virus (MuLV) in DBA/2 cells showed two‐hit kinetics and, at sufficient multiplicities of infection (MOIs), the entire cell population could be productively infected with the restricted virus. Infection of DBA/2 cells with a single particle of B‐tropic (but not with N‐ or NB‐tropic) MuLV which had been inactivated at 43°C rendered the cells permissive to superinfection with B‐tropic MuLV. This effect was time‐dependent, the cells becoming permissive to B‐tropic MuLV by 3 h after the initial infection and regaining their restriction within 18 h. These findings, which are similar to our previous results on the infection of BALB/3T3 ( Fv‐1 b ) cells with N‐tropic MuLV, indicate that two B‐tropic MuLV particles are required for successful infection of a DBA/2 cell in this non‐permissive system. These two particles appear to be functionally different: one temporarily overcomes or “abrogates” Fv‐1 restriction but need not replicate, while the second apparently undergoes a normal replication cycle. Two other Fv‐1 n cell lines, NIH/3T3 and C3H 10T1/2, gave results which were not analogous to those obtained on DBA/2 cells. Even at high MOIs, only about 10–20% of NIH/3T3 or C3H 10T1/2 cells could be infected with B‐tropic MuLV. These quantitative differences in titration patterns indicate that NIH/3T3 and C3H 10T1/2 cells have different mechanisms of Fv‐1 n restriction from that of DBA/2 cells, or, more likely, that they possess other restriction systems in addition to Fv‐1.