Effects of Subtle Changes in the SU Protein of Ecotropic Murine Leukemia Virus on Its Brain Capillary Endothelial Cell Tropism and Interference Properties

Masuda, Mari; Hanson, Charlotte; Alvord, W. Gregory; Hoffman, Paul M.; Ruscetti, Sandra K.; Masuda, Michiaki

doi:10.1006/viro.1996.0017

Cited by 31 publications

(41 citation statements)

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“…Neuropathogenic PVC-211 MuLV and its nonneuropathogenic variant PVFe5 MuLV were grown in Rat-1 or NIH 3T3 fibroblasts in Dulbecco's minimal essential medium (DMEM) plus 10% fetal calf serum (FCS) as previously described (31). Virus samples were collected after 24-h incubation of cells with fresh medium and stored at Ϫ80°C until use.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies using chimeras between PVC-211 MuLV and F-MuLV demonstrated that infection of BCEC is a prerequisite for neurodegeneration induced by PVC-211 MuLV (32). Further studies attributed the ability of PVC-211 MuLV to efficiently infect BCEC to two amino acid changes in the receptor binding domain of its envelope protein (31), which creates a unique heparin binding domain that may allow the virus to bind to proteoglycans on the surface of BCEC (22), aiding infection of this difficult-to-infect cell type. These results suggested that neurodegeneration caused by PVC-211 MuLV is an indirect result of virus infection of blood vessels within the CNS.…”

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confidence: 99%

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Neurodegeneration Induced by PVC-211 Murine Leukemia Virus Is Associated with Increased Levels of Vascular Endothelial Growth Factor and Macrophage Inflammatory Protein 1α and Is Inhibited by Blocking Activation of Microglia

Hanson

Cmarik

et al. 2009

J Virol

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PVC-211 murine leukemia virus (MuLV) is a neuropathogenic retrovirus that has undergone genetic changes from its nonneuropathogenic parent, Friend MuLV, that allow it to efficiently infect rat brain capillary endothelial cells (BCEC). To clarify the mechanism by which PVC-211 MuLV expression in BCEC induces neurological disease, we examined virus-infected rats at various times during neurological disease progression for vascular and inflammatory changes. As early as 2 weeks after virus infection and before any marked appearance of spongiform neurodegeneration, we detected vessel leakage and an increase in size and number of vessels in the areas of the brain that eventually become diseased. Consistent with these findings, the amount of vascular endothelial growth factor (VEGF) increased in the brain as early as 1 to 2 weeks postinfection. Also detected at this early disease stage was an increased level of macrophage inflammatory protein 1␣ (MIP-1␣), a cytokine involved in recruitment of microglia to the brain. This was followed at 3 weeks postinfection by a marked accumulation of activated microglia in the spongiform areas of the brain accompanied by an increase in tissue plasminogen activator, a product of microglia implicated in neurodegeneration. Pathological observations at the end stage of the disease included loss of neurons, decreased myelination, and mild muscle atrophy. Treatment of PVC-211 MuLV-infected rats with clodronate-containing liposomes, which specifically kill microglia, significantly blocked neurodegeneration. Together, these results suggest that PVC-211 MuLV infection of BCEC results in the production of VEGF and MIP-1␣, leading to the vascular changes and microglial activation necessary to cause neurodegeneration.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Neurodegeneration Induced by PVC-211 Murine Leukemia Virus Is Associated with Increased Levels of Vascular Endothelial Growth Factor and Macrophage Inflammatory Protein 1α and Is Inhibited by Blocking Activation of Microglia

Hanson

Cmarik

et al. 2009

J Virol

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“…Stromal cell line MC3T3-G2/PA6 (PA6) (13) was provided by Kevin Holmes and maintained in ␣-minimal essential medium supplemented with 10% FCS. A primary culture of rat brain capillary endothelial cells was prepared and kept as described previously (14).…”

Section: Methodsmentioning

confidence: 99%

Molecular Characterization of the MouseTem1/endosialin Gene Regulated by Cell Density in Vitro and Expressed in Normal Tissues in Vivo

Opavský¹,

Haviernik²,

Jurkovičová³

et al. 2001

Journal of Biological Chemistry

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Human tumor endothelial marker 1/endosialin (TEM1/ endosialin) was recently identified as a novel tumor endothelial cell surface marker potentially involved in angiogenesis, although no specific function for this novel gene has been assigned so far. It was reported to be expressed in tumor endothelium but not in normal endothelium with the exception of perhaps the corpus luteum. Here we describe the cDNA and genomic sequences for the mouse Tem1/endosialin homolog, the identification and characterization of its promoter region, and an extensive characterization of its expression pattern in murine and human tissues and murine cell lines in vitro. The single copy gene that was mapped to chromosome 19 is intronless and encodes a 92-kDa protein that has 77.5% overall homology to the human protein. The remarkable findings are 1) this gene is ubiquitously expressed in normal human and mouse somatic tissues and during development, and 2) its expression at the mRNA level is density-dependent and up-regulated in serum-starved cells. In vitro, its expression is limited to cells of embryonic, endothelial, and preadipocyte origin, suggesting that the wide distribution of its expression in vivo is due to the presence of vascular endothelial cells in all the tissues. The ubiquitous expression in vivo is in contrast to previously reported expression limited to corpus luteum and highly angiogenic tissues such as tumors and wound tissue.

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“…Neuropathogenic PVC-211 and PVF-e5 MuLV, a nonneuropathogenic variant of PVC-211, were grown in NIH 3T3 cells as described previously (30). The viral supernatants had titers of 10 5 to 10 6 PFU/ml as determined by an XC assay (40).…”

Section: Methodsmentioning

confidence: 99%

“…The determinant of the BCEC tropism of PVC-211 MuLV was mapped to two amino acids (G 116 and K 129 ) which lie within the putative receptor binding domain of the envelope surface glycoprotein (SU) (30). Within the CNS, reactive astrocytes and degenerating neurons showed no evidence of virus infection (19).…”

mentioning

confidence: 99%

Expression of Inducible Nitric Oxide Synthase and Elevation of Tyrosine Nitration of a 32-Kilodalton Cellular Protein in Brain Capillary Endothelial Cells from Rats Infected with a Neuropathogenic Murine Leukemia Virus

Jinno-Oue

Wilt

Hanson

et al. 2003

J Virol

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Effects of Subtle Changes in the SU Protein of Ecotropic Murine Leukemia Virus on Its Brain Capillary Endothelial Cell Tropism and Interference Properties

Cited by 31 publications

References 0 publications

Neurodegeneration Induced by PVC-211 Murine Leukemia Virus Is Associated with Increased Levels of Vascular Endothelial Growth Factor and Macrophage Inflammatory Protein 1α and Is Inhibited by Blocking Activation of Microglia

Neurodegeneration Induced by PVC-211 Murine Leukemia Virus Is Associated with Increased Levels of Vascular Endothelial Growth Factor and Macrophage Inflammatory Protein 1α and Is Inhibited by Blocking Activation of Microglia

Molecular Characterization of the MouseTem1/endosialin Gene Regulated by Cell Density in Vitro and Expressed in Normal Tissues in Vivo

Expression of Inducible Nitric Oxide Synthase and Elevation of Tyrosine Nitration of a 32-Kilodalton Cellular Protein in Brain Capillary Endothelial Cells from Rats Infected with a Neuropathogenic Murine Leukemia Virus

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