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1.
J Virol ; 68(8): 5174-83, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8035516

ABSTRACT

Recombinant murine leukemia viruses (MuLVs) from high-leukemia-incidence mouse strains typically acquire pathogenic U3 region sequences from the genome of the endogenous xenotropic virus, Bxv-1. However, a recombinant virus isolated from a leukemic HRS/J mouse and another from a CWD mouse contained U3 regions that lacked genetic markers of Bxv-1. The U3 regions of both recombinants were derived from the endogenous ecotropic virus Env-1 and had retained a single enhancer element. However, compared with that of Emv-1, the U3 region of each of the recombinant viruses contained five nucleotide substitutions, one of which was shared. To determine the biological significance of these substitutions, chimeric ecotropic viruses that contained the U3 region from one of the two recombinant viruses or from Emv-1 were injected into NIH Swiss mice. All three of the chimeric ecotropic viruses were leukemogenic following a long latency. Despite the presence of an enhancer core motif that is known to contribute to the leukemogenicity of the AKR MuLV SL3-3, the HRS/J virus U3 region induced lymphomas only slightly more rapidly than the allelic Emv-1 sequences. The chimeric virus with the U3 region of the CWD recombinant caused lymphomas more frequently and more rapidly than either of the other two viruses. The results support the hypothesis that one or more of the five nucleotide substitutions in the U3 regions of the recombinants contribute to viral pathogenicity. Comparison of DNA sequences suggests that the pathogenicity of the CWD virus U3 region was related to a sequence motif that is shared with Bxv-1 and is recognized by the basic helix-loop-helix class of transcription factors.


Subject(s)
Leukemia Virus, Murine/pathogenicity , 3T3 Cells , Animals , Base Sequence , Cell Line , DNA, Viral , Enhancer Elements, Genetic , Leukemia Virus, Murine/genetics , Leukemia, Experimental/microbiology , Leukemia, Experimental/pathology , Mice , Molecular Sequence Data , Polymerase Chain Reaction , Proviruses/genetics , Rats , Recombination, Genetic , Retroviridae Infections/microbiology , Retroviridae Infections/pathology , Sequence Homology, Nucleic Acid , Tumor Virus Infections/microbiology , Tumor Virus Infections/pathology
2.
J Virol ; 68(6): 3773-83, 1994 Jun.
Article in English | MEDLINE | ID: mdl-8189515

ABSTRACT

Recombinant murine leukemia viruses from the highly leukemic mouse strains AKR, HRS, and C58 usually acquire pathogenic U3 region sequences fro the endogenous xenotropic virus, Bxv-1. However, the majority of tumors from another highly leukemic strain, CWD, contained recombinant viruses that lacked Bxv-1-specific sequences. The nucleotide sequence of the U3 regions of two such CWD recombinants was nearly identical to that of the endogenous ecotropic virus parent Emv-1, but they shared three nucleotide substitutions immediately 3' of the enhancer core. These substitutions were found in recombinant proviruses from about one-third of spontaneous CWD lymphomas as determined by an oligonucleotide hybridization assay of proviral fragments that had been nucleotide substitutions in the CWD viruses were inherited from an endogenous polytropic provirus that is absent in the other highly leukemic strains. On the basis of the results of these and previous studies, we propose that CWD recombinants acquire pathogenic U3 region sequences through recombination with an endogenous polytropic virus or Bxv-1 and that the pathogenicity of these sequences may be related to a sequence motif that is known to bind members of the basic helix-loop-helix class of transcription factors.


Subject(s)
Enhancer Elements, Genetic , Leukemia Virus, Murine/genetics , Lymphoma, B-Cell/microbiology , Lymphoma, T-Cell/microbiology , Animals , Base Sequence , DNA Primers/genetics , DNA, Viral/genetics , Genes, Viral , Leukemia Virus, Murine/pathogenicity , Mice , Molecular Sequence Data , Phenotype , Proviruses/genetics , Recombination, Genetic , Sequence Homology, Nucleic Acid , Species Specificity
3.
J Virol ; 67(1): 294-304, 1993 Jan.
Article in English | MEDLINE | ID: mdl-8380077

ABSTRACT

The genomes of recombinant murine leukemia viruses recovered from HRS/J (type I env recombinants) and CWD (type II env recombinants) mice have distinct envelope gene structures. To better understand the biologic significance of these differences, we examined the differences in the responses of HRS/J and CWD mice to inoculation with an oncogenic type II env recombinant. The CWD recombinant accelerated the onset of lymphoma in both strains, but the disease latency in the HRS/J mice was about 2 months longer. Analysis of the recombinant viruses in the HRS/J tumors revealed that the injected type II env recombinant had recombined in vivo with the endogenous ecotropic viruses to generate secondary recombinants with type I envelope genes. In another set of experiments, comparison of complete or partial DNA sequences of the envelope genes from six recombinant proviruses confirmed that the origins of the sequences that encode an amino-terminal region of the TM envelope protein, p15E, distinguish type I envelope genes from type II. Taken together with the results of previous studies, these observations suggest that the differences in the responses of HRS/J and CWD mice to the oncogenic type II env recombinant resulted from an interaction between the viral TM protein and a host factor expressed in HRS/J mice.


Subject(s)
Genes, Viral/genetics , Leukemia Virus, Murine/genetics , Retroviridae Proteins, Oncogenic/genetics , Selection, Genetic , Viral Envelope Proteins/genetics , Amino Acid Sequence , Animals , Base Sequence , DNA, Recombinant/genetics , DNA, Viral/genetics , Leukemia, Experimental/etiology , Lymphoma/etiology , Mice , Mice, Hairless/microbiology , Mice, Inbred Strains , Molecular Sequence Data , Proviruses/genetics , Sequence Homology, Amino Acid
4.
Med Clin North Am ; 76(3): 549-66, 1992 May.
Article in English | MEDLINE | ID: mdl-1578956

ABSTRACT

Microcytic anemia is defined as the presence of small, often hypochromic, red blood cells in a peripheral blood smear and is usually characterized by a low MCV (less than 83 micron 3). Iron deficiency is the most common cause of microcytic anemia. The absence of iron stores in the bone marrow remains the most definitive test for differentiating iron deficiency from the other microcytic states, ie, anemia of chronic disease, thalassemia, and sideroblastic anemia. However, measurement of serum ferritin, iron concentration, transferrin saturation and iron-binding capacity, and, more recently, serum transferrin receptors may obviate proceeding to bone marrow evaluation. The human body maintains iron homeostasis by recycling the majority of its stores. Disruptions in this balance are commonly seen during menstruation, pregnancy, and gastrointestinal bleeding. Although the iron-absorptive capacity is able to increase upon feedback regarding total body iron stores or erythropoietic activity, this physiologic response is minimal. Significant iron loss requires replacement with iron supplements. The vast majority of patients respond effectively to inexpensive and usually well-tolerated oral iron preparations. In the rare circumstances of malabsorption, losses exceeding maximal oral replacement, or true intolerance, parenteral iron dextran is effective. In either form of treatment, it is necessary to replete iron stores in addition to correcting the anemia.


Subject(s)
Anemia, Hypochromic/diagnosis , Anemia, Hypochromic/drug therapy , Anemia, Hypochromic/etiology , Diagnosis, Differential , Humans , Iron/metabolism , Iron/therapeutic use
5.
J Virol ; 64(11): 5491-9, 1990 Nov.
Article in English | MEDLINE | ID: mdl-2170683

ABSTRACT

The acquisition of U3 region sequences derived from the endogenous xenotropic provirus Bxv-1 appears to be an important step in the generation of leukemogenic recombinant viruses in AKR, HRS, C58, and some CWD mice. We report here that each of three CWD lymphomas produced infectious xenotropic murine leukemia virus related to Bxv-1. In Southern blot experiments, these proviruses hybridized to probes that were specific for the xenotropic envelope and Bxv-1 U3 region sequences. Nucleotide sequence analysis of a cloned CWD xenotropic provirus, CWM-S-5X, revealed that the envelope gene was closely related to but distinct from those of other known xenotropic viruses. In addition, the U3 region of CWM-S-5X contained a viral enhancer sequence that was identical to that found in MCF 247, a recombinant AKR virus that is thought to contain the Bxv-1 enhancer. Finally, restriction enzyme sites in the CWM-S-5X provirus were analogous to those reported within Bxv-1. These results establish that the virus progeny of Bxv-1 have the potential to donate pathogenic enhancer sequences to recombinant polytropic murine leukemia viruses. Interestingly, the three CWD polytropic viruses that were isolated from the same tumor cells that produced the Bxv-1-like viruses had not incorporated Bxv-1 sequences into the U3 region.


Subject(s)
Leukemia Virus, Murine/pathogenicity , Lymphoma/microbiology , Mice, Inbred Strains/microbiology , Amino Acid Sequence , Animals , Base Sequence , Blotting, Southern , Cloning, Molecular , DNA, Neoplasm/genetics , Gene Products, env , Genes, Viral , Genes, env , Leukemia Virus, Murine/genetics , Mice , Molecular Sequence Data , Recombination, Genetic , Restriction Mapping
6.
Virology ; 176(1): 166-77, 1990 May.
Article in English | MEDLINE | ID: mdl-2158688

ABSTRACT

The pathogenic potential of Class II env recombinant murine leukemia viruses (MuLV) found in the high leukemia strain CWD has not been defined. We found that neonatal CWD mice that were injected with the phenotypic mixture of the spontaneous CWD class II env recombinant, CWM-T-15, and the AKR endogenous ecotropic virus, Akv 623, developed non-T-cell lymphomas more rapidly than controls inoculated with either virus alone or with a CWD ecotropic virus. In contrast, CWN-T-25, a class II env MuLV that was recovered from a CWD mouse injected with the AKR ecotropic virus SL3-3, dramatically accelerated the onset of T-cell lymphomas in the same assay. Southern blots of the tumor DNAs from each set of animals revealed the integration of recombinant and ecotropic proviruses. We also found that there were differences in the nucleotide sequences of the viral enhancer elements of the CWD viruses. The results indicate that (1) the two CWD class II env recombinants that were tested contained oncogenic determinants; (2) phenotypic mixing with ecotropic viruses was required for the full expression of the pathogenic potential of the CWM-T-15 recombinant; and (3) the distinct phenotypes of the CWD viruses likely reflected the differences in the origin of the viral enhancer element.


Subject(s)
DNA, Viral/analysis , Enhancer Elements, Genetic , Leukemia Virus, Murine/genetics , Leukemia/genetics , Lymphoma/genetics , Recombination, Genetic , Animals , Base Sequence , Immunoglobulin Light Chains/genetics , Mice , Mice, Inbred Strains , Molecular Sequence Data , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell, alpha-beta
7.
Va Med Q ; 117(7): 311-6, 1990.
Article in English | MEDLINE | ID: mdl-2375179

ABSTRACT

In summary, we present this as the first reported case of both isosporiasis and strongyloidiasis complicating HTLV-I-associated ATLL. Prompt diagnosis and treatment of these parasites in the immunocompromised host are necessary to prevent severe wasting and dehydration. This should also prevent the significant morbidity and mortality associated with dissemination well-described for Strongyloides, and recently seen at autopsy in a patient with isosporiasis. Recurrent infections are common with both organisms, therefore chronic suppressive therapy and prophylactic treatment prior to chemotherapy or steroid administration is warranted.


Subject(s)
Coccidiosis/etiology , Leukemia-Lymphoma, Adult T-Cell/complications , Opportunistic Infections/etiology , Strongyloidiasis/etiology , Female , Humans , Leukemia-Lymphoma, Adult T-Cell/diagnosis , Middle Aged
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