Featured
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Article
| Open Access
Cytosine base editing systems with minimized off-target effect and molecular size
Base editing is promising for gene therapy, but in vivo delivery has been limiting. Here the authors perform structure-based rational engineering of the cytosine base editing system Target-AID to minimise off-target effects and decrease its size.
- Ang Li
- , Hitoshi Mitsunobu
- & Keiji Nishida
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Article
| Open Access
Self-attenuating adenovirus enables production of recombinant adeno-associated virus for high manufacturing yield without contamination
Scalability, yield and quality of recombinant AAVs are a significant issue during manufacture. Here the authors describe a self-inhibiting helper adenovirus strategy that improves outcomes compared to helper-free approaches.
- Weiheng Su
- , Maria I. Patrício
- & Ryan Cawood
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Article
| Open Access
The membrane associated accessory protein is an adeno-associated viral egress factor
Adeno-associated viruses can be secreted in a pre-lytic manner as free or extracellular vesicle (EV)-associated particles. Here, Elmore et al. show that the recently identified membrane-associated accessory protein (MAAP) functions as an AAV egress factor via association to EVs.
- Zachary C. Elmore
- , L. Patrick Havlik
- & Aravind Asokan
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Article
| Open Access
The UPR sensor IRE1α and the adenovirus E3-19K glycoprotein sustain persistent and lytic infections
Adenovirus (AdV) can cause persistent infections, but underlying mechanisms are poorly understood. Here, Prasad et al. show that the AdV glycoprotein E3-19K activates the unfolded protein response sensor IRE1α, and that this triggers a feedforward loop that sustains persistent infection in the presence of interferon.
- Vibhu Prasad
- , Maarit Suomalainen
- & Urs F. Greber
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Article
| Open Access
CryoEM structure of adenovirus type 3 fibre with desmoglein 2 shows an unusual mode of receptor engagement
Human adenoviruses (HAd) cause respiratory, gastrointestinal and ocular infections. Here, the authors provide insights into the early stages of adenovirus infection by determining the cryo-EM structure of the trimeric HAd type 3 fibre knob bound to its cellular receptor human desmoglein 2, which reveals residues critical for HAd-receptor interactions.
- Emilie Vassal-Stermann
- , Gregory Effantin
- & Pascal Fender
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Article
| Open Access
Diversity within the adenovirus fiber knob hypervariable loops influences primary receptor interactions
Adenovirus based (AdV) vectors are promising platforms for therapeutics and vaccines, but receptor usage of serotypes in clinical development remains unclear. Here, based on crystal structures and modeling, Baker et al. show that HAdV-D26/48 fiber knob protein interacts weakly with CAR but not with CD46 or DSG2.
- Alexander T. Baker
- , Alexander Greenshields-Watson
- & Alan L. Parker
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Article
| Open Access
Tridimensional infiltration of DNA viruses into the host genome shows preferential contact with active chromatin
Whether DNA viruses contact specific regions of host genomes or make random contacts is unclear. Here, the authors use Hi-C and show that HBV cccDNA and Ad5 DNA contact preferentially active chromatin at CpG islands for the former and at transcription start sites and enhancers for the latter.
- Pierrick Moreau
- , Axel Cournac
- & Christine Neuveut
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Article
| Open Access
The extracellular interactome of the human adenovirus family reveals diverse strategies for immunomodulation
Viruses interact with their hosts via secreted and membrane-bound proteins to affect host immune responses and virulence. Here the authors contribute to our understanding of this relationship with an extracellular interaction map of human and adenoviral E3 immunomodulatory proteins.
- Nadia Martinez-Martin
- , Sree R. Ramani
- & Lino C. Gonzalez
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Article
| Open Access
MYC-induced reprogramming of glutamine catabolism supports optimal virus replication
Viruses can reprogram glutamine metabolism of host cells to support bioenergetics demands of viral replication. Here the authors show that adenoviral infection leads to enhanced glutamine metabolism through virus-mediated activation of MYC, which is required for optimal progeny virion generation.
- Minh Thai
- , Shivani K. Thaker
- & Heather R. Christofk
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Chemotactic antiviral cytokines promote infectious apical entry of human adenovirus into polarized epithelial cells
Studying how pathogens enter polarized epithelial cells is important for understanding infection. Here, activation of chemokine receptors on the apical membrane of epithelial cells, is shown to engage Src family tyrosine signalling, resulting in relocation of the viral co-receptor αvβ3 to the apical membrane and adenovirus entry.
- Verena Lütschg
- , Karin Boucke
- & Urs F. Greber
Targeting the Retinoblastoma/E2F repressive complex by CDK4/6 inhibitors amplifies oncolytic potency of an oncolytic adenovirus