Positional cloning of the mouse retrovirus restriction gene Fvl

Abstract

VERTEBRATE evolution has taken place against a background of constant retrovirus infection, and much of the mammalian genome consists of endogenous retrovirus-like elements¹. Several host genes have evolved to control retrovirus replication², including Friend-virus-susceptibility-1, Fv1, on mouse chromosome 4 (refs 3, 4). The Fv1 gene acts on murine leukaemia virus at a stage after entry into the target cell but before integration and formation of the provirus⁵. Although restriction is not absolute, Fv1 prevents or delays spontaneous or experimentally induced viral tumours². In vitro, Fv1 restriction leads to an apparent 50–1,000 fold reduction in viral titre⁶. Genetic evidence implicates a direct interaction between the Fv1 gene product and a component of the viral preintegration complex, the capsid protein CA (refs 7–9). We have now cloned Fv1: the gene appears to be derived from the gag region of an endogenous retrovirus unrelated to murine leukaemia virus, implying that the Fv1 protein and its target may share functional similarities despite the absence of nucleotide-sequence homology.