Immunodeficiency and Clonal Growth of Target Cells Induced by Helper-Free Defective Retrovirus

Huang, Ming; Simard, C; Jolicoeur, Paul

doi:10.1126/science.2480643

Cited by 94 publications

(116 citation statements)

References 16 publications

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“…An alternative novel approach of utilizing the Du5H mAIDS virus as an insertional mutagen was developed given the virus preference for infecting mature B-cells (Huang et al, 1989(Huang et al, , 1991. However, mutagenesis studies in the CD1 IgHm-HOX11 Tg mice using the Du5H mAIDS virus were hampered by the decreased susceptibility of CD1 mice to infection with the Du5H mAIDS virus (Huang et al, 1992).…”

Section: C57bl6/j Ighm-hox11 Tg Mice Develop Mature B-cell Malignancimentioning

confidence: 99%

“…However, mutagenesis studies in the CD1 IgHm-HOX11 Tg mice using the Du5H mAIDS virus were hampered by the decreased susceptibility of CD1 mice to infection with the Du5H mAIDS virus (Huang et al, 1992). To overcome this difficulty, the CD1 IgHm-HOX11 Tg mice were backcrossed with C57BL6/J mice for >20 generation to give rise to heterozygous IgHm-HOX11 Tg mice on a mAIDS-susceptible, inbred C57BL6/J genetic background.…”

Section: C57bl6/j Ighm-hox11 Tg Mice Develop Mature B-cell Malignancimentioning

confidence: 99%

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Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

et al. 2006

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Dysregulated expression of the homeobox gene, HOX11 is a frequent etiologic event in T-cell acute lymphoblastic leukemias. HOX11-transgenic mice (IgHl-HOX11 Tg )-expressing HOX11 in the B-cell compartment develop B-cell lymphomas with extended latency. The latency suggests that additional genetic events are required prior to the onset of malignant lymphoma. We report the identification of 17 HOX11 collaborating genes, revealed through their propensity to be targeted in a proviral insertional mutagenesis screen. Seven integrations disrupted genes in mitotic spindle checkpoint control, suggesting that cells with elevated HOX11 expression are especially sensitive to dysregulation of chromosome segregation during mitosis. IgHl-HOX11 Tg primary B-lymphocyte cultures exposed to the aneugenic agents, colchicine and colcemid, exhibited increased incidences of chromosome missegregation as assessed by cytokinesisblock micronucleus assays. Additionally, IgHl-HOX11 Tg cultures were shown to exhibit aberrant bypass of spindle checkpoint arrest, as assessed by the increased presence of cycling cells determined by assessment of DNA content and by BrdU immunolabelling. Western immunoblotting revealed elevated expression of the mitotic effector molecules, cyclin A, cyclin B1 and cdc20 in IgHl-HOX11 Tg cultures. Moreover, spontaneously arising lymphoid neoplasms in IgHl-HOX11 Tg mice frequently exhibit aberrant expression of mitotic regulators, concomitant with increased development of micronuclei, abnormal mitotic checkpoint control and increased incidences of abnormal karyotypes when expanded in culture. Collectively, these findings indicate that abnormal regulation of spindle checkpoint control as a result of HOX11 overexpression leads to a heightened predisposition for development of aneuploidy, contributing to oncogenesis.

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Section: C57bl6/j Ighm-hox11 Tg Mice Develop Mature B-cell Malignancimentioning

confidence: 99%

Section: C57bl6/j Ighm-hox11 Tg Mice Develop Mature B-cell Malignancimentioning

confidence: 99%

Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

et al. 2006

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“…After infection with the LP-BM5 murine leukemia retrovirus isolate, a disease syndrome which includes profound immunodeficiency develops in certain inbred strains of mice such as the highly susceptible C57BL/6 (B6) strain (3,11,26,28,47). By about 3 weeks postinfection (wpi) with LP-BM5, activationrelated events, which include hypergammaglobulinemia (hyperIg) and splenomegaly, become easily detectable in LP-BM5-infected B6 mice.…”

mentioning

confidence: 99%

The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome

Green

Okazaki

Honjo

et al. 2008

J Virol

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“…MAIDS can be induced by helper-free defective virus (9), but in disease induced by the LP-BM5 virus mixture, nonpathogenic, replication-competent ecotropic, and mink cell focus-forming (MCF) viruses serve as helpers for cell-to-cell transmission of the defective genome and are known to accelerate development of disease (5,7).…”

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confidence: 99%

CD19 Signaling Pathways Play a Major Role for Murine AIDS Induction and Progression

Knoetig

Torrey

Naghashfar

et al. 2002

The Journal of Immunology

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Infection of genetically susceptible mice with the LP-BM5 mixture of murine leukemia viruses including an etiologic defective virus (BM5def) causes an immunodeficiency syndrome called murine AIDS (MAIDS). The disease is characterized by interactions between B cells and CD4+ T cells resulting in polyclonal activation of both cell types. It is known that BM5def is expressed at highest levels in B cells and that B cells serve as viral APC. The CD19-CD21 complex and CD22 on the surface of B cells play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival. CD19 integrates positive signals induced by B cell receptor ligation by interacting with the protooncogene Vav, which leads to subsequent tyrosine phosphorylation of this molecule. In contrast, CD22 negatively regulates Vav phosphorylation. To analyze the role of CD19, CD21, Vav, and CD22 in MAIDS, we infected mice deficient in CD19, CD21 (CR2), Vav-1, or CD22 with LP-BM5 murine leukemia viruses. Infected CR2−/− mice developed MAIDS with a time course and severity indistinguishable from that of wild-type mice. In contrast, CD19 as well as Vav-1 deficiency restricted viral replication and suppressed the development of typical signs of MAIDS including splenomegaly, lymphadenopathy, and hypergammaglobulinemia. Finally, CD22 deficiency was found to accelerate MAIDS development. These results provide novel insights into the B cell signaling pathways required for normal induction and progression of MAIDS.

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Immunodeficiency and Clonal Growth of Target Cells Induced by Helper-Free Defective Retrovirus

Cited by 94 publications

References 16 publications

Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

Dysregulated expression of mitotic regulators is associated with B-cell lymphomagenesis in HOX11-transgenic mice

The Programmed Death-1 and Interleukin-10 Pathways Play a Down-Modulatory Role in LP-BM5 Retrovirus-Induced Murine Immunodeficiency Syndrome

CD19 Signaling Pathways Play a Major Role for Murine AIDS Induction and Progression

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