Nucleotide sequence and mode of transmission of the wild mouse ecotropic virus, HoMuLV.

HoMuLV is an NB-tropic wild mouse leukemia virus (MuLV) with ecotropic host range which induces lymphoma, erythroleukemia, and myelogenous leukemia in NIH Swiss mice. Although HoMuLV uses the same cell surface receptor as other ecotropic MuLVs, hybridization studies suggested that the HoMuLV envelope glycoprotein differs from that of other ecotropic MuLVs. We have now molecularly cloned HoMuLV and sequenced its LTR, gag, and env regions. HoMuLV differs markedly from other MuLVs in the LTR U3 region, in the SU protein of env, and in p12gag. U3 contains a single copy of a sequence analogous to the direct repeat found in other LTRs, and this region includes several previously defined protein binding sites. The predicted amino acid sequence for the coding regions of env and gag reveal that p12 and the SU protein show less than 59 and 65% sequence identity, respectively, with those of other MuLVs. A 0.6-kb segment of the 5' region of the HoMuLV env was used as a hybridization probe to examine inbred and wild mouse genomic DNAs for proviral sequences. HoMuLV env sequences were not present in the germline of any of the inbred strains or wild mice examined including the Mus hortulanus mice which harbored infectious virus. Therefore, HoMuLV represents an evolutionarily related, but distinct, subgroup of ecotropic MuLV which is not genetically transmitted in its natural host.