Adenovirus Replication

Guimet, Diana; Hearing, Patrick

doi:10.1016/b978-0-12-800276-6.00003-6

Cited by 5 publications

(3 citation statements)

References 92 publications

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“…The HAdV genome is a linear, double-stranded DNA (dsDNA) genome of approximately 36 kb that is organized in immediate early, early, intermediate, and late transcription units ( 19 ). The onset of viral DNA replication marks the transition from the early to the late phase of infection ( 20 , 21 ).…”

Section: Introductionmentioning

confidence: 99%

A Single Amino Acid Switch in the Adenoviral DNA Binding Protein Abrogates Replication Center Formation and Productive Viral Infection

Boddin

Wilkens

et al. 2022

mBio

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Section: Introductionmentioning

confidence: 99%

A Single Amino Acid Switch in the Adenoviral DNA Binding Protein Abrogates Replication Center Formation and Productive Viral Infection

Boddin

Wilkens

et al. 2022

mBio

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“…Finally, the third-generation AdVs, also called gutless, gutted, helper-dependent, or high-capacity AdVs, have been modified to be devoid of all adenovirus DNA, aside from the sequences mandatory for the packaging of the expression cassette (Figure 2B). This also includes the late-phase transcription regions L1-L5, which are all controlled by the same major late promoter and encode proteins forming the capsid and participating in the assembly, genomic packaging, and regulation of the maturing virions [53].…”

Section: Third-generation Adenovirus Vectorsmentioning

confidence: 99%

Adenoviral Gene Therapy Vectors in Clinical Use—Basic Aspects with a Special Reference to Replication-Competent Adenovirus Formation and Its Impact on Clinical Safety

Leikas,

Ylä-Herttuala,

Hartikainen

2023

IJMS

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Adenoviral vectors are commonly used in clinical gene therapy. Apart from oncolytic adenoviruses, vector replication is highly undesired as it may pose a safety risk for the treated patient. Thus, careful monitoring for the formation of replication-competent adenoviruses (RCA) during vector manufacturing is required. To render adenoviruses replication deficient, their genomic E1 region is deleted. However, it has been known for a long time that during their propagation, some viruses will regain their replication capability by recombination in production cells, most commonly HEK293. Recently developed RCA assays have revealed that many clinical batches contain more RCA than previously assumed and allowed by regulatory authorities. The clinical significance of the higher RCA content has yet to be thoroughly evaluated. In this review, we summarize the biology of adenovirus vectors, their manufacturing methods, and the origins of RCA formed during HEK293-based vector production. Lastly, we share our experience using minimally RCA-positive serotype 5 adenoviral vectors based on observations from our clinical cardiovascular gene therapy studies.

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“…The replication process is localized to the cellular nucleus and starts with the expression of mostly regulatory and non-structural proteins. The propagation of viral DNA is achieved via strand displacement and succeeded by the expression of structural proteins [14].…”

Section: Introductionmentioning

confidence: 99%

Viral interactions with non-homologous end-joining: a game of hide-and-seek

Hristova

Lauer

Ferguson

2020

Journal of General Virology

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There are extensive interactions between viruses and the host DNA damage response (DDR) machinery. The outcome of these interactions includes not only direct effects on viral nucleic acids and genome replication, but also the activation of host stress response signalling pathways that can have further, indirect effects on viral life cycles. The non-homologous end-joining (NHEJ) pathway is responsible for the rapid and imprecise repair of DNA double-stranded breaks in the nucleus that would otherwise be highly toxic. Whilst directly repairing DNA, components of the NHEJ machinery, in particular the DNA-dependent protein kinase (DNA-PK), can activate a raft of downstream signalling events that activate antiviral, cell cycle checkpoint and apoptosis pathways. This combination of possible outcomes results in NHEJ being pro- or antiviral depending on the infection. In this review we will describe the broad range of interactions between NHEJ components and viruses and their consequences for both host and pathogen.

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Adenovirus Replication

Cited by 5 publications

References 92 publications

A Single Amino Acid Switch in the Adenoviral DNA Binding Protein Abrogates Replication Center Formation and Productive Viral Infection

A Single Amino Acid Switch in the Adenoviral DNA Binding Protein Abrogates Replication Center Formation and Productive Viral Infection

Adenoviral Gene Therapy Vectors in Clinical Use—Basic Aspects with a Special Reference to Replication-Competent Adenovirus Formation and Its Impact on Clinical Safety

Viral interactions with non-homologous end-joining: a game of hide-and-seek

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