Sequence analysis of amphotropic and 10A1 murine leukemia viruses: close relationship to mink cell focus-inducing viruses

Abstract

Viral interference studies have demonstrated the existence of four distinct murine leukemia virus (MuLV) receptors on NIH 3T3 mouse cells. The four viral interference groups are ecotropic MuLV; mink cell focus inducing virus (MCF); amphotropic MuLV; and 1OA1, a recombinant derivative of amphotropic MuLV that uses a unique receptor but also retains affinity for the amphotropic MuLV receptor. We report here that 1OAl infects rat and hamster cells, unlike its amphotropic parent. We isolated an infectious molecular clone of 1OAl and present here the sequences of the env genes and enhancer regions of amphotropic MuLV and 1OAl. The deduced amino acid sequences of amphotropic MuLV and 1OAl gp70Su are remarkably similar to those of MCF and xenotropic MuLV (for which mouse cells lack receptors), with 64% amino acids identical in the four groups. We generated a consensus from these comparisons. Further, the differences are largely localized to a few discrete regions: (i) amphotropic MuLV has two short insertions relative to MCF, at residues 87 to 92 and 163 to 169, and (ii) amphotropic MuLV and MCF are totally different in a hypervariable region, which is >30% proline, at residues-253 to 304. 1OAl closely resembles amphotropic MuLV in its N terminus but contains an MCF-type hypervariable region. These results suggest the possibility that receptor specificity is localized in these short variable regions and further that the unique receptor specificity of 1OAl is due to the novel combination of amphotropic MuLV and MCF sequences rather than to the presence of any novel sequences. The Env proteins of ecotropic MuLVs are far more distantly related to those of the other four groups than the latter are to each other. We also found that the enhancer regions of amphotropic MuLV and 1OAl are nearly identical, although 1OAl is far more leukemogenic than amphotropic MuLV.

Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2 mouse model

“…However, these sequences are an abundant source for recombination, when challenged with alternative defective or replication competent viruses. The generation of such recombinants frequently results in viruses with improved virulence and the exchange of the viral env gene [26][27][28]. Of significance to this study, C57BL/10 mice express xenotropic MLV from the Bxv1 locus, which can be a source of viral proteins as well as genetic material [29].…”

An Acidic Cluster of the Cytoplasmic Tail of the RD114 Virus Glycoprotein Controls Assembly of Retroviral Envelopes

“…The phCMV-G plasmid, encoding the VSV-G protein (47), was used as an expression vector construct for the surface glycoproteins derived from the RD114 cat endogenous virus (GenBank accession X87829) (48) and from the 4070A strain of amphotropic MLV (49). The resulting vectors were called phCMV-RD114 and phCMV-MLV and were further modified to generate chimaeric Env that harbour, respectively, the cytoplasmic tails of the MLV and RD114.…”

The dual-function hamster receptor for amphotropic murine leukemia virus (MuLV), 10A1 MuLV, and gibbon ape leukemia virus is a phosphate symporter

“…It is not known how viral infection blocks receptor-specific P i transport. A comparison of the envelope glycoproteins of A-MuLV and 10A1 MuLV with those of GaLVs (approximately 35% amino acid identity) (1,12) provides no basis for defining a region common to these viruses which is not also shared by other members of the Mn 2ϩ -preferring family of oncoretroviruses (1). Therefore, it remains possible and even likely that the A-MuLVs and GaLVs interact with different regions of the EAR receptor.…”