Single Amino Acid Changes in the Murine Leukemia Virus Capsid Protein Gene Define the Target ofFv1Resistance

Abstract

The mouseFv1genetic locus controls resistance to subgroups of ecotropic, MCF, and amphotropic murine leukemia viruses (MuLVs). In addition to the four previously defined alleles ofFv1(Fv1n, Fv1b, Fv1nr, Fv10), we present evidence that the novel restriction pattern characteristic of DBA/2J mice maps to theFv1locus and therefore represents a novel allele, here designatedFv1d.Previous studies had demonstrated that theFv1-mediated viral tropism is determined within the capsid protein gene, and that N- and B-tropic virus capsids differ only in two adjacent amino acids. We introduced various amino acid substitutions at these two sites in the N-tropic AKV MLV capsid gene, and typed resulting viruses for host range on cells carrying all fiveFv1alleles as well as on cells from additional wild mouse species withFv1-like differences in virus susceptibility. Results indicate that alteration of the first of the two amino acids does not alter tropism, but alteration of the second alone is sufficient to convert the N-tropic AKV MLV to a B-tropic virus. Substitution of leucine for arginine at this site produced a virus with an unusual tropism not characteristic of any of the naturally occurring or laboratory strains of MuLV.