Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro

Fredman, J N; Engler, Jeffrey A.

doi:10.1128/jvi.67.6.3384-3395.1993

Cited by 66 publications

(36 citation statements)

References 59 publications

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“…Targeting of the initial replicon is dependent on a dCMP modification of the preterminal protein (pTP), which enables pTP to form a complex with the DNA polymerase and the genome (Temperley and Hay, 1992). PTP mediates targeting of the heterotrimeric complex to the nuclear matrix (Fredman and Engler, 1993), possibly through an interaction with CAD (carbamyl phosphate synthetase, aspartate transcarbamylase and dihydroorotase) (Angeletti and Engler, 1998). Transcription and splicing are mediated by host proteins and viral RNA, and non-SNP RNA splicing factor, hnRNP C proteins, and RNA polymerase II all colocalize with viral RNA in nuclear inclusions.…”

Section: Structure and Location Of Nuclear Inclusions Formed During Amentioning

confidence: 99%

A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

Netherton

Moffat

Brooks

et al. 2007

Advances in Virus Research

200

157

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Virus replication can cause extensive rearrangement of host cell cytoskeletal and membrane compartments leading to the "cytopathic effect" that has been the hallmark of virus infection in tissue culture for many years. Recent studies are beginning to redefine these signs of viral infection in terms of specific effects of viruses on cellular processes. In this chapter, these concepts have been illustrated by describing the replication sites produced by many different viruses. In many cases, the cellular rearrangements caused during virus infection lead to the construction of sophisticated platforms in the cell that concentrate replicase proteins, virus genomes, and host proteins required for replication, and thereby increase the efficiency of replication. Interestingly, these same structures, called virus factories, virus inclusions, or virosomes, can recruit host components that are associated with cellular defences against infection and cell stress. It is possible that cellular defence pathways can be subverted by viruses to generate sites of replication. The recruitment of cellular membranes and cytoskeleton to generate virus replication sites can also benefit viruses in other ways. Disruption of cellular membranes can, for example, slow the transport of immunomodulatory proteins to the surface of infected cells and protect against innate and acquired immune responses, and rearrangements to cytoskeleton can facilitate virus release.

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Section: Structure and Location Of Nuclear Inclusions Formed During Amentioning

confidence: 99%

A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

Netherton

Moffat

Brooks

et al. 2007

Advances in Virus Research

200

157

View full text Add to dashboard Cite

show abstract

“…This is consistent with the observation that replication foci can only be clearly resolved from sites of ssDNA and dsDNA accumulation at later times of infection. Independently of the driving force, the viral genomes probably do not diffuse freely in the nucleus, since Ad DNA is tightly bound to the nuclear matrix throughout the course of infection (Schaack et al, 1990;Fredman and Engler, 1993). The sites of tightest attachment occur in the terminal fragments of the linear viral chromosome and are mediated by the viral terminal protein, which is covalently bound to the 5' end of each DNA strand (Schaack et al, 1990, Fredman andEngler, 1993).…”

mentioning

confidence: 99%

Adenovirus replication and transcription sites are spatially separated in the nucleus of infected cells.

et al. 1994

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We have visualized the intranuclear topography of adenovirus replication and transcription in infected HeLa cells. The results show that viral DNA replication occurs in multiple foci that are highly organized in the nucleoplasm. Pulse‐chase experiments indicate that newly synthesized viral double‐stranded DNA molecules are displaced from the replication foci and spread throughout the nucleoplasm, while the single‐stranded DNA replication intermediates accumulate in adjacent sites. Double‐labelling experiments and confocal microscopy show that replication occurs in foci localized at the periphery of the sites where single‐stranded DNA accumulates. The simultaneous visualization of viral replication and transcription reveals that the sites of transcription are predominantly separated from the sites of replication. Transcription is detected adjacent to the replication foci and extends around the sites of single‐stranded DNA accumulation. These data indicate that newly synthesized double‐stranded DNA molecules are displaced from the replication foci and spread in the surrounding nucleoplasm, where they are used as templates for transcription. Splicing snRNPs are shown to co‐localize with the sites of transcription and to be excluded from the sites of replication. This provides evidence that splicing of viral RNAs occurs co‐transcriptionally and that the sites of viral DNA replication are spatially distinct from the sites of RNA transcription and processing.

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“…127 Ad terminal proteins also bind to the nuclear matrix, which is thought to assist transcription by anchoring the complexes at particular sites within the nucleus. 128 To assess the role of the DNA construct in transcription, a study involving nuclear microinjection of a viral genome versus plasmid DNA indicated that the genome led to 40% increased protein expression. 66 Though the authors hypothesized that nuclear decondensation is a greater factor in transcription than the DNA construct, the current understanding of lipoplex-mediated transfection disputes this, since DNA is believed to be released alone to the cytosol following lipoplex-mediated membranolysis.…”

Section: Gene Expressionmentioning

confidence: 99%

Toward Development of Artificial Viruses for Gene Therapy: A Comparative Evaluation of Viral and Non‐viral Transfection

Douglas¹

2008

Biotechnology Progress

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Problems related to the safety and efficacy of gene therapies have checked the enthusiasm once surrounding this field, though it remains a promising approach for the treatment of numerous diseases. Despite the high transfection efficiencies attainable using viral vectors, manufacturing difficulties, safety concerns, and limitations related to targeting and plasmid size have prompted considerable research into the development of non‐viral vectors. Non‐viral vectors demonstrate low toxicity, low immunogenicity, and ease of manufacture. However, they have not yet achieved the transfection efficiencies displayed by viruses. The inability to explain or predict transfection efficiencies results, in part, from insufficient understanding of the intracellular processes involved in gene delivery. Increasingly, research has been undertaken to probe the processes involved in overcoming the major obstacles to vector‐mediated transfection: (1) internalization, (2) intracellular trafficking, (3) escape to the cytosol, (4) nuclear translocation, and (5) gene transcription/expression. This paper reviews and compares the pathways and techniques involved in successful viral and non‐viral transfection. In addition, this review provides evidence that non‐viral vector development has been pursued successfully thus far, producing systems capable of evading almost all major obstacles to transfection. Evaluating the abilities of non‐viral and viral vectors to overcome specific cellular barriers reveals that the greatest advantage of viral vectors may be related to viral DNA, which is transcribed considerably more efficiently than plasmid DNA. Further study in this area should enable the development of non‐viral vectors that transfect as efficiently as viral vectors.

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Adenovirus precursor to terminal protein interacts with the nuclear matrix in vivo and in vitro

Cited by 66 publications

References 59 publications

A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

A Guide to Viral Inclusions, Membrane Rearrangements, Factories, and Viroplasm Produced During Virus Replication

Adenovirus replication and transcription sites are spatially separated in the nucleus of infected cells.

Toward Development of Artificial Viruses for Gene Therapy: A Comparative Evaluation of Viral and Non‐viral Transfection

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