The high leukemogenic potential of Gross passage A murine leukemia virus maps in the region of the genome corresponding to the long terminal repeat and to the 3' end of env

Abstract

The Gross passage A murine leukemia virus (MuLV) is a highly leukemogenic, ecotropic fibrotropic retrovirus. Its genome is similar to that of other nonleukemogenic ecotropic fibrotropic MuLVs but differs at the 3' end and in the long terminal repeat. To determine whether these modifications were related to its leukemogenic potential, we constructed a viral DNA recombinant in vitro with cloned infectious DNA from this highly leukemogenic Gross passage A MuLV and from a weakly leukemogenic endogenous BALB/c B-tropic MuLV. Infectious viruses, recovered after microinjection of murine cells with recombinant DNA, were injected into newborn mice. We show here that the Gross passage A 1.35-kilobase-pair KpnI fragment (harboring part of gp70, all of p15E, and the long terminal repeat) is sufficient to confer a high leukemogenic potential to this recombinant.

Genesis of Kirsten murine sarcoma virus: sequence analysis reveals recombination points and potential leukaemogenic determinant on parental leukaemia virus genome

“…The nucleotide and deduced amino acid sequence of the p15 env protein of KiMLV is shown in fig. 3, ccmpared to the corresponding regions of the AKV and Gross A MLVs (10,15). The KiMLV sequences appear to be very similar to those of the other two viruses, which is consistent with our previous cbservations (9).…”

“…Within the p15 env dcmiain, DesGroseilliers et al have previously noted only a single position at which an amino acid is camn to the leukaemogenic Gross A and Mbloney MLVs, but different in the nonleukaemogenic AKV (10). This occurs at amino acid position 44 in fig.…”

“…CYs 6LU SER AR6 6LU END 6ROSS A T6T 6SA TCA C6T SM''' NLV same pentanucletide sequence occurs at positions 1227-1231, and 1239-1243 in KiMLV and at positions 1227-1231, 1232-1236, and 1241-1245 in KiMSV. Identification of the 1eukaemogenic determinants of KiMLV A region of the genare encampassing the p15 env and adjacent LTR sequences has been unambiguiously identified as confering high leukaemic potential to the Gross A MLV (10). Thus a ocmparison of this region in the non-leukaemigenic AKV with those in the leukaemogenic Gross A and KiMLV genames, should identify candidate determinants confering leukaemogenicity.…”

“…3 Amino acid sequence of KiMLV p15 env. The sequence is carpared with AKV MLV p15 env (15) and with the coding region of Gross A MV previously implicated as harbouring leukaemogenic detenants (10). Nucleotides and amino acids are nuibered starting at the first position in the pi5E coding sequence.…”

The exogenous form of Jaagsiekte retrovirus is specifically associated with a contagious lung cancer of sheep

“…A putative NF-1 motif in exogenous JSRV LTR (nucleotides 7220 to 7223), which overlaps the exogenous-specific PCR primer P5, is altered and/or lost in the endogenous LTRs, and two tandemly repeated sequences (positions 7347 to 7365 and 7366 to 7384 in the JSRV sequence [43]) appear to be lost by means of an insertion of 30 nucleotides in the endogenous U3. Differences in the nucleotide sequences in these regions could potentially diminish the LTR function (8,9,11,12,17,22,23,26,31,40) and thus reduce the pathogenicity of enJSRVs compared with the exogenous counterpart, as demonstrated in other retroviral systems.…”