Leukemogenesis by Gross passage A murine leukemia virus: expression of viruses with recombinant env genes in transformed cells.

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.

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confidence: 53%

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

DesGroseillers¹,

Villemur²,

Jolicoeur³

1983

“…Like the parental MuLV, the virus recovered was leukemogenic, indicating unambiguously that the ecotropic MuLV component of Gross A MuLV stock harbors sequences responsible for leukemogenicity. Lately, experimental evidence was presented that MCF MuLV plays a role in the development of AKR leukemia (10,20,29), and XC-, dualtropic viruses related to the MCF MuLV were isolated from Gross passage A virus extracts (10). Our results do not favor an etiological role for any putative MCF MuLV that .…”

Section: Discussionmentioning

confidence: 99%

“…AKR mice spontaneously develop thymic lymphoma at a very high frequency at 6 to 9 months of age (12,17). Recombinant leukemogenic murine leukemia viruses (MuLVs), the mink cell focus-inducing (MCF) viruses, have been isolated from these preleukemic and leukemic AKR mouse thymomas (20) and are thought to be involved in the disease process (8,10,29). These are XCand have a xenotropic or dualtropic host range.…”

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confidence: 99%

“…Serial passages of these C3H thymoma cell-free extracts in C3H mice enhanced the leukemogenic potential of this virus, which was designated Gross passage A virus (16). This preparation appears to contain a mixture of ecotropic, xenotropic, and recombinant dualtropic MuLVs (10). One viral isolate of Gross passage A MuLV that was propagated and cloned in vitro on NIH cells retained its leukemogenic potential (6).…”

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confidence: 99%

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

Villemur¹,

Rassart²,

DesGroseillers³

et al. 1983

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.

“…First, several leukemogenic AKR viruses with ecotropic host range and Akv-like gp7O gene sequences have been found to differ from Akv virus only in the 3' end of pl5E and in the U3 E-ANF1 region (25). These viruses may undergo further recombination in vivo to generate viruses with non-Akv gp7O gene sequences (10). Second, the expression of ecotropic viruses with recombinant p15E-U3 sequences precedes the expression of viruses with non-Akv gp7O gene sequences or polytropic viruses during the development of spontaneous thymic leukemia in AKR/J mice (31).…”

Section: An Tmentioning

confidence: 99%

Thymic epithelial genotype influences the production of recombinant leukemogenic retroviruses in mice

Datta¹,

Thomas²,

Nicklas³

et al. 1983

By using T, oligonucleotide fingerprinting and mapping techniques, we analyzed the genomic structure of retroviruses produced by thymocytes and splenocytes of reciprocal bone marrow-and thymus-grafted chimeras. We found that the genetic factor(s) derived from NZB mice that suppresses the development of thymic leukemia in (AKR x NZB)F1 mice also prevents the formation of recombinant leukemogenic viruses and the expression of preleukemic changes in the (AKR x NZB)F1 thymocytes. The NZB mouse gene or genes appeared to exert this suppressive effect by acting on the thymic reticuloepithelial cells and not on the thymic lymphocytes of (AKR x NZB)Fl hybrids. Prospective studies with thymic epithelial grafts from young mice showed that the AKR thymic epithelium could mediate the formation and expression of leukemogenic recombinant viruses and preleukemic changes in thymocytes that lead to the development of thymic leukemia, whereas the (AKR x NZB)Fl thymic epithelium was deficient in this regard. Our results also confirmed a previous observation that during in vivo generation of recombinant leukemogenic viruses, the acquisition of polytropic virus-related sequences in the 3' portion of the plSE gene and the U3 region and in the 5' part of the gp7O gene can occur independently.