Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To probe the genetic basis of disease specificity of nondefective murine type C viruses, we are constructing recombinants in vitro between molecular clones of Friend murine leukemia virus (Fr-MuLV) and Moloney murine leukemia virus (Mo-MuLV). Fr-MuLV induces erythroleukemias when injected into newborn NFS mice, whereas Mo-MuLV almost invariably induces T-cell lymphomas. We find that a recombinant whose genome is derived primarily from Fr-MuLV but which has 621 nucleotides of Mo-MuLV information at its 3' end induces almost exclusively thymic lymphomas. The sequences derived from Mo-MuLV include 99 nucleotides encoding the carboxyl terminus of Prp15E, the origin of DNA +-strand synthesis, all of the U3 region, and 36 nucleotides of the R portion of the long terminal repeat. When the segment of Mo-MuLV was removed and replaced with the comparable segment from Fr-MuLV, the virus was again erythroblastosis-inducing. These results, in conjunction with studies from other laboratories [Laimins, L. A., Khoury, G., Gorman, C., Howard, B. & Gruss, P. (1982) Proc. Natl. Acad. Sci. USA 79, 6453-6457], suggest that transcriptional signals in U3 may determine tissue tropism and hence influence disease specificity ("targeting") of murine leukemia viruses.
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PMID:Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. 630 22

A recombinant DNA clone, named AL10, that contains murine leukemia virus (MuLV) related sequences was isolated from BALB/c mouse chromosomal DNA and examined in detail. Restriction endonuclease mapping revealed that the 10.5 kbp EcoRI insert consists of a 3.6 kbp left flanking cellular DNA region and a 6.9 kbp MuLV-related region that has a typical proviral LTR-gag-pol-env structure up to the EcoRI site in the env gene region. Comparison of the AL10 map with ecotropic and xenotropic virus isolates revealed many common restriction sites in the LTR and pol gene regions, but much fewer in the leader and gag regions. A stretch of 1,700 nucleotides containing the cellprovirus junctional region was sequenced and revealed transcriptional consensus signals and other structural features characteristic of MuLV LTRs, as well as two distinctive features: (a) a sequence of approximately 170 bp with direct and inverted terminal repeats not seen in infectious MuLV LTRs was identified in the U3 region between the "enhancer" region and the "CAT" box. This novel segment or its homologous sequences appear to be present in most of the endogenous MuLV-related LTRs and in other chromosomal locations of the mouse (b) The tRNA primer binding site is not complementary to proline tRNA, the primer for all known MuLVs, but is a 17/18 match with rat glutamine tRNA. The integration site of AL10 provirus was in a unique DNA region but contained an "Alu"-like short interdispersed repeat in the 5' adjacent cellular region. The AL10 proviral integration found in BALB/c was also apparent in RFM, AKR and SENCAR mouse cells but not in cells of NFS/N, C3H, HRS/J, SC-1, and a California Lake Casitas wild mouse.
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PMID:A novel sequence segment and other nucleotide structural features in the long terminal repeat of a BALB/c mouse genomic leukemia virus-related DNA clone. 631 May 6

SL3-3 is a potent leukemogenic retrovirus that closely resembles the non-leukemogenic virus Akv. Both viruses were isolated from AKR mice, have ecotropic host ranges, and form plaques in the XC assay. They differ at only 1 to 2% of the nucleotides in the viral genomes but differ markedly in virulence properties. SL3-3 induces leukemia in a high percentage of inoculated AKR, C3H, CBA, and NFS mice, whereas Akv does not induce disease in any of these strains. To determine which region of the genome accounts for the leukemogenic potential of SL3-3, we constructed recombinant genomes between molecular clones of SL3-3 and Akv. Recombinant, viral DNA genomes were cloned and then were transfected onto NIH 3T3 fibroblasts to generate infectious virus. The recombinant viruses were tested for leukemogenicity in AKR/J, CBA/J, and C3Hf/Bi mice. We localized the primary leukemogenic determinant to a 3.8-kilobase fragment of the SL3-3 genome containing the viral long terminal repeat, 5' untranslated sequences, gag gene, and 5', 30% of the pol gene. Reciprocal recombinants containing the equivalent region from Akv, linked to the env gene and the remainder of the pol gene from SL3-3, did not induce leukemia. We conclude that the primary virulence determinant of SL3-3 lies outside the region of the genome that encodes the envelope proteins gp70 and p15E.
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PMID:Localization of the leukemogenic determinants of SL3-3, an ecotropic, XC-positive murine leukemia virus of AKR mouse origin. 631 68

A new isolate of a murine erythroblastosis-inducing spleen focus-forming virus (Cas SFFV), derived from the wild mouse ecotropic murine leukemia virus Cas-Br-M, was further characterized after the production of a nonproducer cell line. When rescued from the nonproducer cells with a helper murine leukemia virus, the Cas SFFV induced rapid splenic enlargement and focus formation when inoculated into adult NFS/N mice. The Cas SFFV nonproducer cell line was also utilized to compare the envelope-related glycoprotein of Cas SFFV with gp52s from three strains of Friend SFFV. Cas SFFV was found to encode a 50,500-dalton glycoprotein (gp50) distinct in size to the envelope-related glycoproteins of the Friend SFFVs. The Cas SFFV was also compared in RNA blot hybridization studies. The genomic viral RNA of Cas SFFV was found to be slightly larger than two polycythemia-inducing strains of Friend SFFV and markedly larger than the anemia-inducing strain. Further comparisons between the SFFVs were made by examining their transforming capabilities in an in vitro erythroid burst assay. The erythroid bursts induced by Cas SFFV and the anemia-inducing strain of Friend SFFV showed similarities in their erythropoietin requirements. This study supports our recent observations that Cas SFFV is biologically similar to the anemia-inducing strain of Friend SFFV yet biochemically distinct from all Friend SFFVs.
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PMID:Cas spleen focus-forming virus. II. Further biological and biochemical characterization. 631 69

In addition to the known induction of xenotropic endogenous virus in B-mitogen-stimulated murine lymphocyte cultures, distinguishable defective viruses were also induced in different mouse strains (NFS/N, 129, BALB/c). AKR cells produced xenotropic virus and also, in contrast to BALB/c, ecotropic virus. The drug bromodeoxyuridine appeared to have differential effects on virus expression, amplifying xenotropic virus induction but inhibiting the spontaneous production of the ecotropic virus in AKR cultures and of the defective virus in NFS/N cells. Infecting stimulated BALB/c or AKR cultures with Friend leukaemia virus resulted in the production of ecotropic-xenotropic pseudotype viruses, indicating that the infecting ecotropic virus replicates in the cells in which xenotropic virus is induced. No pseudotypes or recombinants were observed following infection of spleen cells releasing defective viruses. Friend leukaemia virus and xenotropic virus with an ecotropic envelope replicated equally well in stimulated lymphocytes from the different strains examined. Taken together, these findings indicate that the non-infectious viruses are encoded by defective proviruses, rather than resulting from faulty, host cell-controlled, virus maturation.
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PMID:Phenotypic mixing of retroviruses in mitogen-stimulated lymphocytes: analysis of xenotropic and defective endogenous mouse viruses. 631 77

Cas-Br-M, a cloned ecotropic murine leukemia virus (MuLV) of wild mouse origin that induces both neurogenic hindlimb paralysis and lymphomas, was injected into NFS/N inbred mice neonatally. Then the mice were observed for the development of neurologic disease and tumors. All mice manifested neurologic abnormalities by 6 months of age, and 58% of the animals died with hematopoietic neoplasms. The tumors included T- and B-cell lymphomas, lymphoblastic lymphoma, erythroleukemias, myelogenous leukemias, and a megakaryocytic leukemia. Cas-Br-M thus appeared to be unique among ecotropic MuLV in inducing a wide spectrum of hematopoietic tumors.
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PMID:Histologic and cell surface antigen studies of hematopoietic tumors induced by Cas-Br-M murine leukemia virus. 631 93

The sequence of 363 nucleotides near the 3' end of the pol gene and 564 nucleotides from the 5' terminus of the env gene in an endogenous murine leukemia viral (MuLV) DNA segment, cloned from AKR/J mouse DNA and designated as A-12, was obtained. For comparison, the nucleotide sequence in an analogous portion of AKR mink cell focus-forming (MCF) 247 MuLV provirus was also determined. Sequence features unique to MCF247 MuLV DNA in the 3' pol and 5' env regions were identified by comparison with nucleotide sequences in analogous regions of NFS -Th-1 xenotropic and AKR ecotropic MuLV proviruses. These included (i) an insertion of 12 base pairs encoding four amino acids located 60 base pairs from the 3' terminus of the pol gene and immediately preceding the env gene, (ii) the deletion of 12 base pairs (encoding four amino acids) and the insertion of 3 base pairs (encoding one amino acid) in the 5' portion of the env gene, and (iii) single base substitutions resulting in 2 MCF247 -specific amino acids in the 3' pol and 23 in the 5' env regions. Nucleotide sequence comparison involving the 3' pol and 5' env regions of AKR MCF247 , NFS xenotropic, and AKR ecotropic MuLV proviruses with the cloned endogenous MuLV DNA indicated that MCF247 proviral DNA sequences were conserved in the cloned endogenous MuLV proviral segment. In fact, total nucleotide sequence identity existed between the endogenous MuLV DNA and the MCF247 MuLV provirus in the 3' portion of the pol gene. In the 5' env region, only 4 of 564 nucleotides were different, resulting in three amino acid changes between AKR MCF247 MuLV DNA and the endogenous MuLV DNA present in clone A-12. In addition, nucleotide sequence comparison indicated that Moloney-and Friend-MCF MuLVs were also highly related in the 3' pol and 5' env regions to the cloned endogenous MuLV DNA. These results establish the role of endogenous MuLV DNA segments in generation of recombinant MCF viruses.
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PMID:Nucleotide sequence analysis establishes the role of endogenous murine leukemia virus DNA segments in formation of recombinant mink cell focus-forming murine leukemia viruses. 632 17

Six new B lineage lymphomas of NFS mice established in primary tissue culture were examined for a number of phenotypic, functional, virologic, and molecular genetic characteristics. Two of the tumors and their cloned derivatives bore surface markers characteristic of B cells, whereas four tumors resembled pre-B cells. One of the B cell and two of the pre-B cell lymphomas had rearrangements of both heavy and light chain immunoglobulin genes, confirming their designation as B-lineage lymphomas. All the tumors but one were Ly-1+, indicating that Ly-1 may be expressed by some pre-B cells as well as some B cells. In addition, one pre-B cell lymphoma was Mac-1+. MCF murine leukemia viruses obtained from two of the tumors did not accelerate development of B-lineage lymphomas in NFS mice.
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PMID:A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. 633 Feb 1

A family of recombinant mink cell focus-forming viruses (MCF) was derived by inoculation of NFS mice with a Friend murine leukemia virus, and their genomes were analyzed by RNase T1-resistant oligonucleotide fingerprinting. The viruses were obtained from the thymuses and spleens of preleukemic and leukemic animals and were evaluated for dualtropism and oncogenicity. All these isolates induced cytopathic foci on mink cells but could be classified into two groups based on their relative infectivities for SC-1 (mouse) or mink (ATCC CCL64) cells. One group of Friend MCFs (F-MCFs) (group I) exhibited approximately equal infectivities for SC-1 and mink cells, whereas a second group (group II) infected mink cells 1,000- to 10,000-fold more efficiently than SC-1 cells. Structural analyses of the F-MCFs revealed that group I and group II viruses correlated with recombination of Friend murine leukemia virus with two distinct, but closely related, endogenous NFS proviral sequences. No correlation was found between the type of F-MCF and the tissue of origin or the disease state of the animal. Furthermore, none of the F-MCF isolates were found to be oncogenic in NFS/N or AKR/J mice. F-MCFs of both groups underwent extensive substitution of ecotropic sequences, involving much of the gag and env genes of group I F-MCFs and most of the gag, pol, and env genes of group II F-MCFs. All F-MCF isolates retained the 3' terminal U3 region of Friend murine leukemia virus. Comparison of the RNAs of the F-MCFs with RNAs of MCFs derived from NFS.Akv-1 or NFS.Akv-2 mice indicated that the F-MCFs were derived from NFS proviral sequences which are distinct from the sequences contained in NFS.Akv MCF isolates. This result suggested that recombination with particular endogenous proviral sequences to generate MCFs may be highly specific for a given murine leukemia virus.
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PMID:Generation of mink cell focus-forming viruses by Friend murine leukemia virus: recombination with specific endogenous proviral sequences. 642 51

The production of recombinant retroviruses is an important episode in the natural history of thymic leukaemia in AKR and HRS/J (hr/hr) mices. These viruses apparently originate from ecotropic and xenotropic precursors in the late preleukaemic stage of the disease. Analyses of their structural proteins and genomic oligonucleotides indicate that they arise by recombination of env genes of the precursor viruses. This event leads to a viral envelope glycoprotein (gp70) with some peptides that have features of the gp70 glycoproteins of ecotropic and xenotropic viruses, and others that are unique for each recombinant virus. The former property explains the broad host range of recombinant viruses, and hence their designation as dual tropic or polytropic viruses. It has been postulated that the unique aspect of each recombinant's gp70 determines the phenotypes of leukaemic cells. Polytropic viruses may be highly thymotropic. Their systemic administration results in an infection that confines itself virtually to the thymus. Moreover, these viruses are leukaemogenic whereas their precursors are not, or only weakly so. The leukaemogenicity of polytropic viruses is, however, restricted to certain inbred strains of mice. The HRS/J isolate PTV-1 is leukaemogenic in HRS/J and CBA/J mice, but not in SWR/J or NIH/Swiss mice. The experiments described here demonstrate that a single dominant gene permits infection by thymocytes by a leukaemogenic polytrophic virus. CBA/J mice, which develop thymic leukaemia after infection by this virus, posesses this gene, whereas leukaemia-resistant NFS mice lack it.
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PMID:A single dominant gene determines susceptibility to a leukaemogenic recombinant retrovirus. 725 16


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