Adenovirus-Mediated Transfer of the Amphotropic Retrovirus Receptor cDNA Increases Retroviral Transduction in Cultured Cells

Lieber, André; Peeters, Marie‐Jeanne T. F. D. Vrancken; Kay, Mark A.

doi:10.1089/hum.1995.6.1-5

Cited by 44 publications

(20 citation statements)

References 27 publications

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“…We plan to perform colony assays or, preferably, repopulation assays in SCID-NOD mice with gutless vectors (68) or integrating ⌬Ad.AAV vectors devoid of all viral genes (40) generated based on Ad5GFP/F35 chimeric capsids. Alternatively, gutless, retargeted vectors could be used to transiently express a retroviral receptor on CD34 ϩ cells to increase their susceptibility to infection with retroviral vectors based on an approach that we have published earlier (38).…”

Section: This Implies That Viral Replication Analyses Performed With mentioning

confidence: 99%

Efficient Gene Transfer into Human CD34 ⁺ Cells by a Retargeted Adenovirus Vector

Shayakhmetov

Papayannopoulou

Stamatoyannopoulos

et al. 2000

J Virol

341

321

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Section: This Implies That Viral Replication Analyses Performed With mentioning

confidence: 99%

Efficient Gene Transfer into Human CD34 ⁺ Cells by a Retargeted Adenovirus Vector

Shayakhmetov

Papayannopoulou

Stamatoyannopoulos

et al. 2000

J Virol

341

321

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“…(12). Primary mouse hepatocytes were isolated by collagenase perfusion (29) and cultured in Primaria dishes (Corning Corp., Acton, MA) in William's E medium supplemented with 10% fetal bovine serum. Ad5L1 and Ad5‫ء‬F express luciferase and green fluorescent protein (GFP); and Ad5L2 and Ad5/35L express ␤-galactosidase from identical expression cassettes.…”

mentioning

confidence: 99%

Adenovirus Binding to Blood Factors Results in Liver Cell Infection and Hepatotoxicity

Shayakhmetov

Gaggar

et al. 2005

J Virol

376

422

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Adenoviruses (Ad) are efficient vehicles for gene delivery in vitro and in vivo. Therefore, they are a promising tool in gene therapy, particularly in the treatment of cancer and cardiovascular diseases. However, preclinical and clinical studies undertaken during the last decade have revealed a series of problems that limit both the safety and efficacy of Ad vectors, specifically after intravenous application. Major obstacles to clinical use include innate toxicity and Ad sequestration by nontarget tissues. The factors and mechanisms underlying these processes are poorly understood. The majority of intravenously injected Ad particles are sequestered by the liver, which in turn causes an inflammatory response characterized by acute transaminitis and vascular damage. Here, we describe a novel pathway that is used by Ad for infection of hepatocytes and Kupffer cells upon intravenous virus application in mice. We found that blood factors play a major role in targeting Ad vectors to hepatic cells. We demonstrated that coagulation factor IX and complement component C4-binding protein can bind the Ad fiber knob domain and provide a bridge for virus uptake through cell surface heparan sulfate proteoglycans and low-density lipoprotein receptor-related protein. An Ad vector, Ad5mut, which contained mutations in the fiber knob domain ablating blood factor binding, demonstrated significantly reduced infection of liver cells and liver toxicity in vivo. This study contributes to a better understanding of adenovirus-host interactions for intravenously applied vectors. It also provides a rationale for novel strategies to target adenovirus vector to specific tissues and to reduce virus-associated toxicity after systemic application.

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“…Retrovirus vectors were generated as described previously (34). Ecotropic virus generated following transient transfection of the vectors into PE501 cells was used to infect the amphotropic packaging line PA317.…”

Section: Methodsmentioning

confidence: 99%

Nuclear Import of Moloney Murine Leukemia Virus DNA Mediated by Adenovirus Preterminal Protein Is Not Sufficient for Efficient Retroviral Transduction in Nondividing Cells

Lieber

Kay

2000

J Virol

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Moloney murine leukemia virus (MoMLV)-derived vectors require cell division for efficient transduction, which may be related to an inability of the viral DNA-protein complex to cross the nuclear membrane. In contrast, adenoviruses (Ad) can efficiently infect nondividing cells. This property may be due to the presence of multiple nuclear translocation signals in a number of Ad proteins, which are associated with the incoming viral genomes. Of particular interest is the Ad preterminal protein (pTP), which binds alone or in complex with the Ad polymerase to specific sequences in the Ad inverted terminal repeat. The goal of this study was to test whether coexpression of pTP with retroviral DNA carrying pTP-binding sites would facilitate nuclear import of the viral preintegration complex and transduction of quiescent cells. In preliminary experiments, we demonstrated that the karyophylic pTP can coimport plasmid DNA into the nuclei of growth-arrested cells. Retroviral transduction studies were performed with G 1 /S-arrested LTA cells or stationary-phase human primary fibroblasts. These studies demonstrated that pTP or pTP-Ad polymerase conferred nuclear import of retroviral DNA upon arrested cells when the retrovirus vector contained the corresponding binding motifs. However, pTP-mediated nuclear translocation of MoMLV DNA in nondividing cells was not sufficient for stable transduction. Additional cellular factors activated during S phase or DNA repair synthesis were required for efficient retroviral integration.Integration of viral DNA into the host chromosome is an essential step in the retrovirus life cycle. With their remarkably efficient ability to integrate, retrovirus vectors are an important tool in obtaining stable gene expression in vitro and in vivo (37, 65). However, the most commonly used and as yet best-characterized vectors based on mammalian C-type retroviruses cannot transduce quiescent cells, which often represent the targets for gene therapy approaches (20,38,43,63).After entry of the retroviral core into the cytoplasm, the retroviral genome is reverse transcribed by using enzymatic activities associated with the incoming virion. The resulting double-stranded linear viral DNA is associated with viral proteins, forming a large nucleoprotein complex. To complete the retroviral life cycle, this preintegration complex must be translocated to the nucleus. The mechanisms of nuclear transport appear to differ among different retrovirus subfamilies and host cells (for a review, see reference 8). For Moloney murine leukemia virus (MoMLV)-derived vectors, it is believed that breakdown of the nuclear membrane during mitosis is necessary to allow access of the preintegration complex to chromosomal DNA. This is supported by two lines of evidence: (i) inhibitors, which delay the onset of mitosis, delay integration as well (3, 33, 38); and (ii) MoMLV proviruses segregate into only one daughter cell during the first mitotic division after infection, implying that integration occurs after DNA replication (19,43). T...

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Adenovirus-Mediated Transfer of the Amphotropic Retrovirus Receptor cDNA Increases Retroviral Transduction in Cultured Cells

Cited by 44 publications

References 27 publications

Efficient Gene Transfer into Human CD34 ⁺ Cells by a Retargeted Adenovirus Vector

Efficient Gene Transfer into Human CD34 ⁺ Cells by a Retargeted Adenovirus Vector

Adenovirus Binding to Blood Factors Results in Liver Cell Infection and Hepatotoxicity

Nuclear Import of Moloney Murine Leukemia Virus DNA Mediated by Adenovirus Preterminal Protein Is Not Sufficient for Efficient Retroviral Transduction in Nondividing Cells

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Adenovirus-Mediated Transfer of the Amphotropic Retrovirus Receptor cDNA Increases Retroviral Transduction in Cultured Cells

Cited by 44 publications

References 27 publications

Efficient Gene Transfer into Human CD34 + Cells by a Retargeted Adenovirus Vector

Efficient Gene Transfer into Human CD34 + Cells by a Retargeted Adenovirus Vector

Adenovirus Binding to Blood Factors Results in Liver Cell Infection and Hepatotoxicity

Nuclear Import of Moloney Murine Leukemia Virus DNA Mediated by Adenovirus Preterminal Protein Is Not Sufficient for Efficient Retroviral Transduction in Nondividing Cells

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Efficient Gene Transfer into Human CD34 ⁺ Cells by a Retargeted Adenovirus Vector

Efficient Gene Transfer into Human CD34 ⁺ Cells by a Retargeted Adenovirus Vector