scholarly journals Friend murine leukemia virus-induced leukemia is associated with the formation of mink cell focus-inducing viruses and is blocked in mice expressing endogenous mink cell focus-inducing xenotropic viral envelope genes.

1981 ◽  
Vol 154 (3) ◽  
pp. 907-920 ◽  
Author(s):  
S Ruscetti ◽  
L Davis ◽  
J Feild ◽  
A Oliff
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Envelope ◽  
Envelope Gene ◽  
Related Protein ◽  
Newborn Mice ◽  
Endogenous Expression ◽  
Mink Cell ◽  
Resistant Strains ◽  
Murine Leukemia

In these studies, we have shown data that are consistent with the hypothesis that mink cell focus-inducing viruses (MCF) play an important role in the generation of an erythroproliferative disease developing after injection of certain strains of newborn mice with ecotropic Friend murine leukemia virus (F-MuLV). Resistance to this disease is correlated with the endogenous expression of an MCF/xenotropic virus-gp70-related protein that may interfere with the replication or spread of MCF viruses. These ideas are supported by the following observations: (a) after infection with F-MuLV, only 6/13 strains of mice-developed disease, and studies with crosses between susceptible and resistant strains indicated that resistance was dominant. Although F-MuLV was shown to replicate equally well in all strains tested, viruses coding for MCF-specific viral envelope proteins could be detected only in the spleens of mice from strains that were resistant to F-MuLV-induced disease and not in the spleens of mice from strains that were resistant to F-MuLV-induced disease; (b) a Friend MCF (Fr-MCF) virus isolated from the spleen of an F-MuLV-infected mouse from a susceptible strain induced the same erythroproliferative disease when injected as an appropriate pseudotype into mice from susceptible but not resistant strains of mice; and (c) resistant but not susceptible strains of mice endogenously express MCF/xenotropic virus-related envelope glycoproteins that may be responsible for resistance by blocking receptors for MCF viruses. These results not only indicate that Fr-MCF virus is a crucial intermediate in the induction of disease by F-MuLV, but also suggest that a novel gene, either an MCF/xenotropic virus-related envelope gene or a gene controlling its expression, is responsible for resistance to erythroleukemia induced by F-MuLV.

scholarly journals Susceptibility of BALB/c mice carrying various DBA/2 genes to development of Friend murine leukemia virus-induced erythroleukemia.

1985 ◽  
Vol 162 (5) ◽  
pp. 1579-1587 ◽  
Author(s):  
S Ruscetti ◽  
R Matthai ◽  
M Potter
Keyword(s):  
Structural Gene ◽  
Envelope Glycoprotein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Regulatory Gene ◽  
Constitutive Expression ◽  
Newborn Mice ◽  
Unique Protein ◽  
Mink Cell ◽  
Murine Leukemia

Using a series of BALB/c mice congenic for various DBA/2 genes, we were able to establish that DBA/2 mice carry a gene on chromosome 5, at or near the Rmcfr locus, that plays a major role in resistance to early erythroleukemia induced by injection of Friend murine leukemia virus (F-MuLV) into newborn mice. The fact that this gene controls the replication of mink cell focus-inducing (MCF) viruses strengthens the case for these viruses playing a crucial role in the development of erythroleukemia, since failure to replicate MCF viruses results in resistance to early erythroleukemia. The expression of the Rmcfr gene is correlated with the constitutive expression of an MCF virus-related envelope glycoprotein that apparently blocks the receptor for MCF viruses, preventing their spread. Thus, the Rmcfr gene is either a structural gene for this unique protein, which can block the receptor for MCF viruses, or is a regulatory gene that controls expression of such a structural gene. Although the Rmcfr gene is clearly involved in resistance to the early erythroleukemia induced by F-MuLV, it appears to have no effect on the late myeloid, lymphoid or erythroid diseases that appear in DBA/2 and other strains of mice after injection of F-MuLV, consistent with data indicating that replication of MCF viruses is not required for the development of these late diseases. Our studies with congenic and backcross mice also indicate that, in addition to the Rmcfr gene, other genes of DBA/2 origin may contribute to resistance to F-MuLV-induced early erythroleukemia by mechanisms other than blocking the replication of MCF viruses.

scholarly journals Induction of Endoplasmic Reticulum Stress in Thymic Lymphocytes by the Envelope Precursor Polyprotein of a Murine Leukemia Virus during the Preleukemic Period

2007 ◽  
Vol 81 (8) ◽  
pp. 4374-4377 ◽  
Author(s):  
Fayth K. Yoshimura ◽  
Xixia Luo
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Envelope ◽  
Virus Envelope ◽  
Thymic Lymphocyte ◽  
Mink Cell ◽  
Induced Apoptosis ◽  
Murine Leukemia

ABSTRACT Infection of thymic lymphocytes by a mink cell focus-forming murine leukemia virus induces apoptosis during the preleukemic period of lymphomagenesis. In this study, we observed that during this period, the viral envelope precursor polyprotein accumulated to high levels in thymic lymphocytes from mice inoculated with virus. Envelope accumulation occurred with the same kinetics as the induction of endoplasmic reticulum (ER) stress, which resulted in the upregulation of the 78-kDa glucose-regulated protein (GRP78). In thymic lymphomas, GRP78 levels were higher than those in virus-infected preleukemic cells, and GRP58 was upregulated. These results suggest that Env precursor accumulation induces ER stress, which participates in thymic lymphocyte apoptosis. The subsequent upregulation of ER chaperone proteins GRP78 and GRP58 may contribute to rescuing cells from virus-induced apoptosis.

scholarly journals Moloney Murine Leukemia Virus-Induced Preleukemic Thymic Atrophy and Enhanced Thymocyte Apoptosis Correlate with Disease Pathogenicity

1999 ◽  
Vol 73 (3) ◽  
pp. 2434-2441 ◽  
Author(s):  
Christine Bonzon ◽  
Hung Fan
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Annexin V ◽  
Moloney Murine Leukemia Virus ◽  
Wild Type ◽  
Thymic Atrophy ◽  
Thymocyte Apoptosis ◽  
Mink Cell ◽  
Nih Swiss ◽  
Murine Leukemia

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.

scholarly journals Amplified env and gag products on AKR cells. Origin from different murine leukemia virus genomes.

1980 ◽  
Vol 151 (4) ◽  
pp. 975-979 ◽  
Author(s):  
J S Tung ◽  
E Fleissner
Keyword(s):  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Mouse Strains ◽  
Type Antigen ◽  
Mink Cell ◽  
Virus Expression ◽  
Virus Genomes ◽  
Akr Mice ◽  
Ecotropic Virus ◽  
Murine Leukemia

Thymocytes of AKR mice express two species of gp70, the envelope glycoprotein of murine leukemia virus (MuLV), encoded by the env gene. One is denoted Ec+ gp70 in reference to the type-antigen Ec and association with ecotropic virus. The other, Ec- gp70, resembles gp70 found also on thymocytes of mouse strains that are not overt producers of MuLV, and has no evident relation to ecotropic virus. Expression of Ec- gp70 type, but not of Ec+ gp70 type, is amplified with age on AKR thymocytes. In contrast, viral core polyproteins, encoded by the gag gene and simultaneously amplified with age, appear to be related to ecotropic virus. These observations imply selective amplification of products of env and gag genes from two sorts of provirus, a phenomenon which may be connected to the dual genetic origin of recombinant mink-cell-focus inducing viruses in AKR mice.

scholarly journals THE VIRAL ENVELOPE GLYCOPROTEIN OF MURINE LEUKEMIA VIRUS AND THE PATHOGENESIS OF IMMUNE COMPLEX GLOMERULONEPHRITIS OF NEW ZEALAND MICE

1974 ◽  
Vol 140 (4) ◽  
pp. 1011-1027 ◽  
Author(s):  
Takashi Yoshiki ◽  
Robert C. Mellors ◽  
Mette Strand ◽  
J. T. August
Keyword(s):  
New Zealand ◽  
Immune Complex ◽  
Envelope Glycoprotein ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Viral Envelope ◽  
High Concentration ◽  
Immune Complex Glomerulonephritis ◽  
Viral Envelope Glycoprotein ◽  
Murine Leukemia

The use of monospecific antisera for the analysis by radioimmunoassay and immunofluorescence study of two major viral proteins, gp69/71 and p30 of murine leukemia virus, that could be of significance in the pathogenesis of immune complex glomerulonephritis of mice, particularly NZB and B/WF1 hybrid mice, yielded the following conclusions. A remarkably high concentration of viral envelope glycoprotein, gp69/71, was detected in the spleen and serum of New Zealand mice (NZB, NZW, B/WF1, and W/BF1); the concentration in the spleen was 10-fold greater than that found in AKR mice and 30-fold greater than that present in C57BL/6 mice. The gp69/71 was deposited along with bound immunoglobulins, apparently as an immune complex, in the diseased kidneys of mice, and the glomerular site and extent of deposition of gp69/71 was related to the severity of the glomerulonephritis. This study suggests that the pathogenesis of immune complex glomerulonephritis (and vasculitis) in mice is related to the expression of this specific viral envelope glycoprotein and to the host immune response to this protein.

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