A conserved mechanism of retrovirus restriction in mammals

The murine Fv1 gene restricts infection by N- or B-tropic murine leukemia v iruses at a postentry, preintegration stage. The Fv1-sensitive viruses prev iously used for the study of Fv1 encode an ecotropic envelope gene and thus only infect rodent cells. Consequently, the study of Fv1 restriction has b een carried out solely in mice and murine cell lines. By infection with ret roviral Vectors containing N- or B-tropic core and pantropic vesicular stom atitis virus-G envelope protein, we now demonstrate that cell lines derived from various mammalian species, including humans, have an Fv1-like retrovi rus restriction function, preventing N-tropic vector infection. Like Fv1, r estriction is directed at amino acid 110 of the viral capsid protein. In co ntrast to Fv1, the novel restriction is characterized by the absence of rev erse-transcribed viral DNA, We speculate that these activities have been se lected for by retroviral epidemics in the distant past.