Evolution of the Retroviral Restriction Gene <i>Fv1</i>: Inhibition of Non-MLV Retroviruses

<div><p>Fv1 is the prototypic restriction factor that protects against infection by the murine leukemia virus (MLV). It was first identified in cells that were derived from laboratory mice and was found to be homologous to the <i>gag</i> gene of an endogenous retrovirus (ERV). To understand the evolution of the host restriction gene from its retroviral origins, <i>Fv1</i>s from wild mice were isolated and characterized. Most of these possess intact open reading frames but not all restricted N-, B-, NR-or NB-tropic MLVs, suggesting that other viruses could have played a role in the selection of the gene. The Fv1s from <i>Mus spretus</i> and <i>Mus caroli</i> were found to restrict equine infectious anemia virus (EIAV) and feline foamy virus (FFV) respectively, indicating that Fv1 could have a broader target range than previously thought, including activity against lentiviruses and spumaviruses. Analyses of the <i>Fv1</i> sequences revealed a number of residues in the C-terminal region that had evolved under positive selection. Four of these selected residues were found to be involved in the novel restriction by mapping studies. These results strengthen the similarities between the two capsid binding restriction factors, <i>Fv1</i> and TRIM5α, which support the hypothesis that <i>Fv1</i> defended mice against waves of retroviral infection possibly including non-MLVs as well as MLVs.</p></div>