TY - DATA T1 - Evolution of the Retroviral Restriction Gene Fv1: Inhibition of Non-MLV Retroviruses PY - 2014/03/06 AU - Melvyn W. Yap AU - Emily Colbeck AU - Scott A. Ellis AU - Jonathan P. Stoye UR - https://plos.figshare.com/articles/dataset/Evolution_of_the_Retroviral_Restriction_Gene_Fv1_Inhibition_of_Non_MLV_Retroviruses/954597 DO - 10.1371/journal.ppat.1003968 L4 - https://ndownloader.figshare.com/files/1410971 L4 - https://ndownloader.figshare.com/files/1410972 L4 - https://ndownloader.figshare.com/files/1410973 KW - Evolutionary biology KW - Evolutionary genetics KW - genetics KW - Gene function KW - Genetic mutation KW - microbiology KW - Virology KW - Viral transmission and infection KW - Viral clearance KW - Animal models of infection KW - Viral replication KW - Virulence factors and mechanisms KW - Host-pathogen interaction KW - retroviral KW - inhibition KW - non-mlv KW - retroviruses N2 - 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 gag gene of an endogenous retrovirus (ERV). To understand the evolution of the host restriction gene from its retroviral origins, Fv1s 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 Mus spretus and Mus caroli 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 Fv1 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, Fv1 and TRIM5α, which support the hypothesis that Fv1 defended mice against waves of retroviral infection possibly including non-MLVs as well as MLVs. ER -