An Engineered Virus Library as a Resource for the Spectrum-wide Exploration of Virus and Vector Diversity

Zhang, Wenli; Fu, Jun; Liu, Jing; Wang, Hailong; Schiwon, Maren; Janz, Sebastian; Schaffarczyk, Lukas; Goltz, Lukas von der; Ehrke‐Schulz, Eric; Dörner, Johannes; Solanki, Manish; Boehme, Philip; Bergmann, Thorsten; Lieber, André; Lauber, Chris; Dahl, Andreas; Petzold, A.; Zhang, Youming; Stewart, A. Francis; Ehrhardt, Anja

doi:10.1016/j.celrep.2017.05.008

Cited by 54 publications

(88 citation statements)

References 55 publications

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“…There are currently 90 accepted genotypes characterized by whole-genome analysis (http:// hadvwg.gmu.edu/) (10)(11)(12); these are parsed into seven species (A to G) based on biological, clinical, and genomic attributes (13). Ironically, they are used as gene and epitope delivery vectors as well as oncolytic agents (14), despite their roles as human pathogens. HAdV is implicated in a wide spectrum of diseases involving the respiratory, ocular, gastrointestinal, and genitourinary systems in humans (13).…”

mentioning

confidence: 99%

A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts

Dehghan

Seto

Liu

et al. 2019

J Virol

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Genomics analysis of a historically intriguing and predicted emergent human adenovirus (HAdV) pathogen, which caused pneumonia and death, provides insight into a novel molecular evolution pathway involving “ping-pong” zoonosis and anthroponosis. The genome of this promiscuous pathogen is embedded with evidence of unprecedented multiple, multidirectional, stable, and reciprocal cross-species infections of hosts from three species (human, chimpanzee, and bonobo). This recombinant genome, typed as HAdV-B76, is identical to two recently reported simian AdV (SAdV) genomes isolated from chimpanzees and bonobos. Additionally, the presence of a critical adenoviral replication element found in HAdV genomes, in addition to genes that are highly similar to counterparts in other HAdVs, reinforces its potential as a human pathogen. Reservoirs in nonhuman hosts may explain periods of apparent absence and then reemergence of human adenoviral pathogens, as well as present pathways for the genesis of those thought to be newly emergent. The nature of the HAdV-D76 genome has implications for the use of SAdVs as gene delivery vectors in human gene therapy and vaccines, selected to avoid preexisting and potentially fatal host immune responses to HAdV. IMPORTANCE An emergent adenoviral human pathogen, HAdV-B76, associated with a fatality in 1965, shows a remarkable degree of genome identity with two recently isolated simian adenoviruses that contain cross-species genome recombination events from three hosts: human, chimpanzee, and bonobo. Zoonosis (nonhuman-to-human transmission) and anthroponosis (human to nonhuman transmission) may play significant roles in the emergence of human adenoviral pathogens.

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mentioning

confidence: 99%

A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts

Dehghan

Seto

Liu

et al. 2019

J Virol

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“…The method of homologous recombination in bacteria has been very successful since it was established two decades ago, and it is still globally popular today. [6][7][8] Recently, new methods, such as direct ligation after digestion with rare-cutter restriction enzyme (especially homing endonuclease), 9 site-specific recombination, bacterial artificial chromosome-based recombination, and even DNA assembly, have been used to construct adenoviral vectors. [10][11][12] Several DNA assembly methods are used across the synthetic biology community, among which the most used method is isothermal or Gibson assembly (after Daniel Gibson who developed the technique).…”

Section: Introductionmentioning

confidence: 99%

Single Plasmid-Based, Upgradable, and Backward-Compatible Adenoviral Vector Systems

Liu¹,

Zhang

et al. 2019

Human Gene Therapy

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Existing adenoviral vector systems have two drawbacks. It is labor-intensive and time-consuming to load a transgene in these systems, and transgene-harboring vectors are dead ends: they cannot be reused to construct a vector carrying another transgene or achieving new characteristics. To conquer these shortcomings, single plasmid-based adenoviral vector systems were constructed where a unique PmeI site was located at the position for insertion of the exogenous gene. The polymerase chain reaction (PCR) amplified transgene could be cloned into PmeI-linearized starting plasmids using one step of Gibson assembly to generate target adenoviral plasmids, which were then ready for virus rescue. This procedure was termed restriction assembly. To expand the application of these systems, two ClaI sites were created upstream and downstream of the fiber gene to generate an upgraded starting plasmid pKAd5f11pABR-EPG. The modified fiber gene, amplified by overlap extension PCR, could be used to substitute the original fiber in pKAd5f11pABR-EPG to generate an adenoviral plasmid with a new fiber by restriction assembly. On the other hand, pKAd5f11pABR-EPG was also a starting adenoviral plasmid for expressing other transgenes.In conclusion, easy-to-use and upgradable adenoviral vector systems are introduced here, which offer extensive versatility and can serve as a basic platform and functional component library for the synthetic biology of adenoviral vectors.

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“…More recently, the most advanced RecET‐mediated linear–linear homologous recombination (LLHR) system was applied to incorporate the adenoviral genome into easy‐to‐manipulate plasmids. This step was followed by rapid adenoviral genome modification by λ Red‐mediated linear–circular homologous recombination (LCHR) . Using this cloning strategy, 34 different human Ad types were cloned from purified Ad virions and genomic DNA of infected cells .…”

Section: Techniques For Getting Access To the Natural Diversity Of Humentioning

confidence: 99%

“…This step was followed by rapid adenoviral genome modification by λ Red‐mediated linear–circular homologous recombination (LCHR) . Using this cloning strategy, 34 different human Ad types were cloned from purified Ad virions and genomic DNA of infected cells . Furthermore, in that same study a high‐throughput strategy was used to insert reporter genes into the Ad genomes.…”

Section: Techniques For Getting Access To the Natural Diversity Of Humentioning

confidence: 99%

State‐of‐the‐art human adenovirus vectorology for therapeutic approaches

et al. 2019

Self Cite

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Human adenoviruses (Ads) have long been studied in the basic virology field and are exploited as vectors for gene therapy, vaccination, and oncolytic therapy. Ads are usually mild pathogens, but they can cause severe infections and symptoms in immunocompromised individuals. Ads show a large natural diversity and a broad spectrum of hosts. However, replication-competent and replication-deficient Ad vectors with therapeutic applications have been built mainly starting from human Ad type 5, because generating vectors from other human and animal Ads has proven challenging. This review provides an updated overview of vectors that are not derived from human Ad type 5. We discuss genetic engineering techniques for getting access to the natural diversity of human Ads and for vectorization of alternative Ad types. A catalogue of currently available vectorized human Ads and translational applications thereof is also compiled. We conclude with a perspective on Ad vectorology that looks into the future of Ad vectors in translational medicine.

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An Engineered Virus Library as a Resource for the Spectrum-wide Exploration of Virus and Vector Diversity

Cited by 54 publications

References 55 publications

A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts

A Zoonotic Adenoviral Human Pathogen Emerged through Genomic Recombination among Human and Nonhuman Simian Hosts

Single Plasmid-Based, Upgradable, and Backward-Compatible Adenoviral Vector Systems

State‐of‐the‐art human adenovirus vectorology for therapeutic approaches

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