Molecular cloning of viral DNA from leukemogenic Gross passage A murine leukemia virus and nucleotide sequence of its long terminal repeat

Abstract

The viral DNA genome of the leukemogenic Gross passage A virus was cloned in phage Charon 21A as an infectious molecule. The virus recovered by transfection with this infectious DNA was ecotropic, N-tropic, fibrotropic, and XC+. It was leukemogenic when reinjected into newborn SIM mice, indicating that ecotropic murine leukemia virus (MuLV) from an AKR mouse thymoma can harbor leukemogenic sequences. Its restriction map was similar to that of nonleukemogenic AKR MuLV, its putative parent, but differed at the 3' end and in the long terminal repeat (LTR). The nucleotide sequence of the Gross A virus LTR was identical to the AKR MuLV LTR sequence (Van Beveren et al., J. Virol. 41:542-556, 1982) in U5, R, and part of U3. All differences between both LTRs were found in U3. Only one copy of the U3 tandem direct repeat was conserved in the Gross A virus LTR, and it was rearranged by the insertion of a 36-base-pair sequence and by five point mutations. Only one additional point mutation common to several oncogenic MuLVs was present in U3. These structural changes in the U3 LTR and at the 3' end of the genome may be related to the leukemogenicity of this virus.

Identification of the SL3-3 virus enhancer core as a T-lymphoma cell-specific element

“…These differences include single base pair changes, substitutions, and deletions of longer stretches of nucleotides (19). Some of the differences that distinguish SL3-3 from Akv are also present in the LTR of thymomagenic Gross passage A virus (19,38). One that is common to both SL3-3 and Gross passage A virus resides in a block of nucleotides related to the consensus sequence element known as the enhancer core, which was first identified in the simian virus 40 (SV40) enhancer (18,40) and is important for its activity (15,40,44).…”

Identification of a variant of gross leukemia virus that induces disease in mice inoculated as adults.

“…The leukemogenic viruses isolated from AKR thymomas have been found to be dualtropic mink cell focus-forming (MCF) viruses (6,7) although some appear to be ecotropic (8,9). These viruses contain gag, pol, and env regions but no transforming genes (9)(10)(11).…”

“…The leukemogenic viruses isolated from AKR thymomas have been found to be dualtropic mink cell focus-forming (MCF) viruses (6,7) although some appear to be ecotropic (8,9). These viruses contain gag, pol, and env regions but no transforming genes (9)(10)(11). In this respect, they are similar to avian leukosis virus (ALV), which induces B cell transformation in chickens, apparently by a promoter-insertion mechanism in which the proviral genome integrates adjacent to c-mvc resulting in the increased transcription of this gene (12)(13)(14).…”

“…Alternatively, the leukemogenicity in adult mice of WB91-GV may be associated with certain unique changes that have occurred in the 3' (env-U3) region of the virus genome, either as the result of mutation or recombination with some endogenous virus. Differences within this region have previously been demonstrated to affect the leukemogenicity and potency of retroviruses (9,10).…”

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

“…Fig. 4 Nucleotide sequence of the KiM4V LTR and 3' adjacent region showing a carparison with KiMSV, AKV MLV (16) and Gross A NLV (17). The numbering of nucleotides is continuous with that in fig.…”