Deoxyribonucleic acid-dependent ribonucleic acid poly-merases from spleen of uninfected and Rauscher murine leukemia virus-infected NIH swiss mice

ABSTRACT Moloney murine leukemia virus (M-MuLV) is a replication-competent, simple retrovirus that induces T-cell lymphoma with a mean latency of 3 to 4 months. During the preleukemic period (4 to 10 weeks postinoculation) a marked decrease in thymic size is apparent for M-MuLV-inoculated mice in comparison to age-matched uninoculated mice. We were interested in studying whether the thymic regression was due to an increased rate of thymocyte apoptosis in the thymi of M-MuLV-inoculated mice. Neonatal NIH/Swiss mice were inoculated subcutaneously (s.c.) with wild-type M-MuLV (approximately 105 XC PFU). Mice were sacrificed at 4 to 11 weeks postinoculation. Thymic single-cell suspensions were prepared and tested for apoptosis by two-parameter flow cytometry. Indications of apoptosis included changes in cell size and staining with 7-aminoactinomycin D or annexin V. The levels of thymocyte apoptosis were significantly higher in M-MuLV-inoculated mice than in uninoculated control animals, and the levels of apoptosis were correlated with thymic atrophy. To test the relevance of enhanced thymocyte apoptosis to leukemogenesis, mice were inoculated with the Mo+PyF101 enhancer variant of M-MuLV. When inoculated intraperitoneally, a route that results in wild-type M-MuLV leukemogenesis, mice displayed levels of enhanced thymocyte apoptosis comparable to those seen with wild-type M-MuLV. However, in mice inoculated s.c., a route that results in attenuated leukemogenesis, significantly lower levels of apoptosis were observed. This supported a role for higher levels of thymocyte apoptosis in M-MuLV leukemogenesis. To examine the possible role of mink cell focus-forming (MCF) recombinant virus in raising levels of thymocyte apoptosis, MCF-specific focal immunofluorescence assays were performed on thymocytes from preleukemic mice inoculated with M-MuLV and Mo+PyF101 M-MuLV. The results indicated that infection of thymocytes by MCF virus recombinants is not required for the increased level of apoptosis and thymic atrophy.

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The humoral immune response of NIH Swiss and SWR/J mice to vaccination with formalinized AKR or Gross murine leukemia virus.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.74.1.343 ◽

1977 ◽

Vol 74 (1) ◽

pp. 343-347 ◽

Cited By ~ 8

Author(s):

J. C. Lee ◽

J. N. Ihle ◽

R. Huebner

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Murine Leukemia Virus ◽

Leukemia Virus ◽

Humoral Immune ◽

Nih Swiss ◽

Murine Leukemia

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Helper-independent mink cell focus-inducing strains of Friend murine type-C virus: potential relationship to the origin of replication-defective spleen focus-forming virus.

Journal of Experimental Medicine ◽

10.1084/jem.148.3.639 ◽

1978 ◽

Vol 148 (3) ◽

pp. 639-653 ◽

Cited By ~ 39

Author(s):

D H Troxler ◽

E Yuan ◽

D Linemeyer ◽

S Ruscetti ◽

E M Scolnick

Keyword(s):

Murine Leukemia Virus ◽

Leukemia Virus ◽

Potential Relationship ◽

Virus Complex ◽

Mink Cell ◽

Type C ◽

Nih Swiss ◽

Relationship Of ◽

Ecotropic Virus ◽

Murine Leukemia

Recent studies have indicated that both the replication-defective spleen focus-forming virus (SFFV) in the Friend virus complex and the helper-independent mink cell focus-inducing (MCF) viruses derived from AKR-murine leukemia virus (MuLV) are env gene recombinants between ecotropic virus and xenotropic virus. In an attempt to isolate additional env gene recombinants between Friend murine leukemia virus (F-MuLV) and xenotropic virus, we have inoculated cloned ecotropic F-MuLV into newborn NIH Swiss mice and analyzed MuLV released from preleukemic and leukemic spleens of infected mice. Two helper-independent MCF strains of F-MuLV have been isolated. Like the previously described AKR-MCF viruses, the Friend MCF viruses are env gene recombinants between an ecotropic virus (F-MuLV) and a mouse xenotropic virus, as shown by host range, interference pattern, and tryptic peptide analysis of the gp70s of these MuLV. Furthermore, RNA from the Friend MCF viruses hybridizes completely to cDNAsffv, a nucleic acid probe which detects that portion of SFFV which was not derived from P-MuLV. The ability to isolate replicating MCF viruses derived from F-MuLV FURTHER strengthens the parallels between the Friend erythroleukemia system and the AKR thymic leukemia system. Finally, the potential relationship of helper-independent env gene recombinants between F-MuLV and xenotropic virus to be highly leukemogenic SFFV is discussed.

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Characterization of mouse cellular deoxyribonucleic acid homologous to Abelson murine leukemia virus-specific sequences

Molecular and Cellular Biology ◽

10.1128/mcb.1.8.731-742.1981 ◽

1981 ◽

Vol 1 (8) ◽

pp. 731-742

Author(s):

B Dale ◽

B Ozanne

Keyword(s):

Murine Leukemia Virus ◽

Deoxyribonucleic Acid ◽

Leukemia Virus ◽

Moloney Murine Leukemia Virus ◽

Base Pairs ◽

Noncoding Regions ◽

Abelson Murine Leukemia Virus ◽

Specific Sequences ◽

Murine Leukemia

The genome of Abelson murine leukemia virus (A-MuLV) consists of sequences derived from both BALB/c mouse deoxyribonucleic acid and the genome of Moloney murine leukemia virus. Using deoxyribonucleic acid linear intermediates as a source of retroviral deoxyribonucleic acid, we isolated a recombinant plasmid which contained 1.9 kilobases of the 3.5-kilobase mouse-derived sequences found in A-MuLV (A-MuLV-specific sequences). We used this clone, designated pSA-17, as a probe restriction enzyme and Southern blot analyses to examine the arrangement of homologous sequences in BALB/c deoxyribonucleic acid (endogenous Abelson sequences). The endogenous Abelson sequences within the mouse genome were interrupted by noncoding regions, suggesting that a rearrangement of the cell sequences was required to produce the sequence found in the virus. Endogenous Abelson sequences were arranged similarly in mice that were susceptible to A-MuLV tumors and in mice that were resistant to A-MuLV tumors. An examination of three BALB/c plasmacytomas and a BALB/c early B-cell tumor likewise revealed no alteration in the arrangement of the endogenous Abelson sequences. Homology to pSA-17 was also observed in deoxyribonucleic acids prepared from rat, hamster, chicken, and human cells. An isolate of A-MuLV which encoded a 160,000-dalton transforming protein (P160) contained 700 more base pairs of mouse sequences than the standard A-MuLV isolate, which encoded a 120,000-dalton transforming protein (P120).

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Tissue Distribution and Timing of Appearance of Polytropic Envelope Recombinants during Infection with SL3-3 Murine Leukemia Virus or Its Weakly Pathogenic SL3ΔMyb5 Mutant

Journal of Virology ◽

10.1128/jvi.75.1.522-526.2001 ◽

2001 ◽

Vol 75 (1) ◽

pp. 522-526 ◽

Cited By ~ 2

Author(s):

Karen Rulli ◽

Patricia A. Lobelle-Rich ◽

Alla Trubetskoy ◽

Jack Lenz ◽

Laura S. Levy

Keyword(s):

Bone Marrow ◽

Murine Leukemia Virus ◽

Recombinant Virus ◽

Time Course ◽

Leukemia Virus ◽

Transplantable Tumor ◽

Tumor Induction ◽

Recombinant Viruses ◽

Nih Swiss ◽

Murine Leukemia

ABSTRACT A time course analysis was performed to identify the sites of formation and timing of appearance of polytropic recombinant viruses following infection of NIH/Swiss mice with the murine retrovirus SL3-3 murine leukemia virus (SL3) or with a weakly pathogenic mutant termed SL3ΔMyb5. The results indicated that (i) polytropic recombinant viruses occur initially in the thymus of SL3-infected animals, (ii) the timing of appearance of polytropic recombinants in bone marrow is not consistent with their participation in the previously reported formation of transplantable tumor-forming cells at 3 to 4 week postinoculation, and (iii) the efficient generation of recombinant virus is correlated with efficient tumor induction.

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Electron Microscopic Observations on the Ribonucleic Acid of Murine Leukemia Virus

Journal of Virology ◽

10.1128/jvi.4.4.460-474.1969 ◽

1969 ◽

Vol 4 (4) ◽

pp. 460-474 ◽

Cited By ~ 28

Author(s):

Tsuyoshi Kakefuda ◽

John P. Bader

Keyword(s):

Ribonucleic Acid ◽

Murine Leukemia Virus ◽

Leukemia Virus ◽

Electron Microscopic ◽

Murine Leukemia

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Disruption of Hematopoiesis and Thymopoiesis in the Early Premalignant Stages of Infection with SL3-3 Murine Leukemia Virus

Journal of Virology ◽

10.1128/jvi.76.5.2363-2374.2002 ◽

2002 ◽

Vol 76 (5) ◽

pp. 2363-2374 ◽

Cited By ~ 10

Author(s):

Karen Rulli ◽

Jack Lenz ◽

Laura S. Levy

Keyword(s):

Bone Marrow ◽

Murine Leukemia Virus ◽

Time Course ◽

Infected Animal ◽

Leukemia Virus ◽

Long Terminal Repeats ◽

Early Stages ◽

Tumor Outgrowth ◽

Nih Swiss ◽

Murine Leukemia

ABSTRACT A time course analysis of SL3-3 murine leukemia virus (SL3) infection in thymus and bone marrow of NIH/Swiss mice was performed to assess changes that occur during the early stages of progression to lymphoma. Virus was detectable in thymocytes, bone marrow, and spleen as early as 1 to 2 weeks postinoculation (p.i.). In bone marrow, virus infection was detected predominantly in immature myeloid or granulocytic cells. Flow cytometry revealed significant reductions of the Ter-119+ and Mac-1+ populations, and significant expansions of the Gr-1+ and CD34+ populations, between 2 and 4 weeks p.i. Analysis of colony-forming potential confirmed these findings. In the thymus, SL3 replication was associated with significant disruption in thymocyte subpopulation distribution between 4 and 7 weeks p.i. A significant thymic regression was observed just prior to the clonal outgrowth of tumor cells. Proviral long terminal repeats (LTRs) with increasing numbers of enhancer repeats were observed to accumulate exclusively in the thymus during the first 8 weeks p.i. Observations were compared to the early stages of infection with a virtually nonpathogenic SL3 mutant, termed SL3ΔMyb5, which was shown by real-time PCR to be replication competent. Comparison of SL3 with SL3ΔMyb5 implicated certain premalignant changes in tumorigenesis, including (i) increased proportions of Gr-1+ and CD34+ bone marrow progenitors, (ii) a significant increase in the proportion of CD4− CD8− thymocytes, (iii) thymic regression prior to tumor outgrowth, and (iv) accumulation of LTR enhancer variants. A model in which disrupted bone marrow hematopoiesis and thymopoiesis contribute to the development of lymphoma in the SL3-infected animal is discussed.

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