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Article
| Open Access
Leafhopper salivary vitellogenin mediates virus transmission to plant phloem
A plant virus induces and hijacks vitellogenin (Vg) of insect vector into virus-induced exosomes for release together from salivary glands to plant phloem, where the Vg suppresses H2O2 burst, facilitating insect feeding and viral transmission.
- Yanfei Wang
- , Chengcong Lu
- & Qian Chen
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Article
| Open Access
The AAV capsid can influence the epigenetic marking of rAAV delivered episomal genomes in a species dependent manner
rAAV vectors vary in their effectiveness between species, making it difficult to predict clinical outcomes. Here authors show that AAV capsid proteins influence the vector epigenomic state in cells, and that a single amino acid change in the vector can alter the vector epigenome and hence transgene expression levels between species.
- Adriana Gonzalez-Sandoval
- , Katja Pekrun
- & Mark A. Kay
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Article
| Open Access
Polerovirus N-terminal readthrough domain structures reveal molecular strategies for mitigating virus transmission by aphids
The authors present structures of plant polerovirus NRTD proteins that protrude from the viral capsid and show that the purified NRTD can inhibit insect transmission and act as a bioinsecticide, providing a blueprint for control of related viruses.
- Carl J. Schiltz
- , Jennifer R. Wilson
- & Joshua S. Chappie
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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
Chemogenetic ON and OFF switches for RNA virus replication
Therapeutic application of RNA viruses requires tight control over viral activity. Here the authors design a regulatory switch that enables control over activity with clinically approved HIV protease inhibitors.
- E. Heilmann
- , J. Kimpel
- & D. von Laer
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Article
| Open Access
Viral gene drive in herpesviruses
Current gene drive strategies are restricted to sexually reproducing species. Here the authors develop a gene drive in herpesviruses that allows the spread of an engineered trait through a viral population.
- Marius Walter
- & Eric Verdin
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Article
| Open Access
Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties
Adeno-associated viruses (AAVs) are vehicles for gene therapy in humans, but currently only a limited amount of AAV serotypes is available. Here, the authors identify a novel AAV, AAVv66, and demonstrate enhanced production yields, virion stability, and CNS transduction compared to the clinically approved serotype AAV2.
- Hung-Lun Hsu
- , Alexander Brown
- & Guangping Gao
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Article
| Open Access
Zika virus noncoding RNA suppresses apoptosis and is required for virus transmission by mosquitoes
The function on subgenomic flaviviral RNA (sfRNA) in the mosquito vector is not well understood. Here, Slonchak et al. show that sfRNA affects virus-induced apoptosis and dissemination of ZIKV in Aedes aegypti mosquitoes, suggesting a role of sfRNA in Zika virus replication and transmission.
- Andrii Slonchak
- , Leon E. Hugo
- & Alexander A. Khromykh
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Article
| Open Access
Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins
A current challenge in genome editing is delivering Cas9 and sgRNA into target cells. Here the authors engineer a delivery system based on murine leukemia virus-like particles loaded with Cas9-sgRNA ribonucleoproteins to induce efficient genome editing in both cell culture and in vivo in mouse.
- Philippe E. Mangeot
- , Valérie Risson
- & Emiliano P. Ricci
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Article
| Open Access
RNA-guided transcriptional silencing in vivo with S. aureus CRISPR-Cas9 repressors
Repression of gene transcription using CRISPR-Cas9 has been achieved in vitro but not for delivery into adult animal models. Here, the authors use AAV8 to deliver the transcriptional repressor dSaCas9KRAB to the cholesterol regulator Pcsk9, and show repression up to 24 weeks and reduced cholesterol levels in mice.
- Pratiksha I. Thakore
- , Jennifer B. Kwon
- & Charles A. Gersbach
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Article
| Open Access
Blood meal acquisition enhances arbovirus replication in mosquitoes through activation of the GABAergic system
Transmission of many human viruses depends on replication in their mosquito vectors. Here, Zhu et al. show that glutamic acid digested from the blood meal activates GABA signaling, resulting in suppression of antiviral innate immunity and increased virus replication in mosquitoes.
- Yibin Zhu
- , Rudian Zhang
- & Gong Cheng
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Article
| Open Access
Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy
Viruses trigger potent cytotoxic T cell responses, whereas anti-tumour immunity has been difficult to establish. Here the authors engineer a replicating viral delivery system for tumour-associated antigens, which induces alarmin release, innate activation and protective anti-tumour immunity in mice.
- Sandra M. Kallert
- , Stephanie Darbre
- & Daniel D. Pinschewer
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Article
| Open Access
Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity
Oncolytic viruses induce a variety of immune targets in the infected tumours. Here, the authors show that Newcastle Disease Virus (NDV) upregulates the inducible co-stimulator (ICOS) on T cells and that intratumoral targeting of ICOS with engineered NDV in combination with CTLA-4 blockade induces systemic anti-tumour immunity in mice.
- Dmitriy Zamarin
- , Rikke B. Holmgaard
- & James P. Allison
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Article
| Open Access
Substrate specificity and transport mechanism of amino-acid transceptor Slimfast from Aedes aegypti
Anautogenous mosquitoes need to obtain essential amino acids from a blood meal for reproduction. Here, the authors examine the amino acid transporter Slimfast from the yellow-fever mosquito and describe both its specificity and mechanism of action.
- Dmitri Y. Boudko
- , Hitoshi Tsujimoto
- & Immo A. Hansen
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Article
| Open Access
AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia
Cell-based screening assays allow functional testing of chemicals but do not mimic the in vivosituation well. Here, the authors report a method for the discovery of secreted cytoprotective factors in mice and use it to demonstrate that the hormone ghrelin protects cardiac muscle from ischaemic damage.
- Giulia Ruozi
- , Francesca Bortolotti
- & Mauro Giacca
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Article
| Open Access
Modelling breast cancer requires identification and correction of a critical cell lineage-dependent transduction bias
Clinical breast cancers predominantly present luminal features, but experimental models are essentially basal. Here the authors show that luminal cells are significantly less susceptible to viral transduction, and present methods to analyse and overcome the bias in heterogeneous populations.
- William C. Hines
- , Paul Yaswen
- & Mina J. Bissell
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Article
| Open Access
Population genomics supports baculoviruses as vectors of horizontal transfer of insect transposons
Horizontal transfer of DNA is common among eukaryotes but the vectors involved remain elusive. Here, Gilbert et al. show high frequency of in vivotransposition from the cabbage looper moth into genomes of a baculovirus, suggesting that viruses can act as vectors of horizontal transfer between animals.
- Clément Gilbert
- , Aurélien Chateigner
- & Richard Cordaux
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Article
| Open Access
Drawing a high-resolution functional map of adeno-associated virus capsid by massively parallel sequencing
Adeno-associated viruses (AAV) are promising gene transfer vectors for human gene therapy. Here, the authors report a high-throughput, sequencing-based method for characterizing amino acid function in AAV capsids and highlight the potential of this method for improving capsid design.
- Kei Adachi
- , Tatsuji Enoki
- & Hiroyuki Nakai
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Axonal and subcellular labelling using modified rabies viral vectors
Viral vectors can be used both to map and manipulate neural circuits in vivo; however, their use is limited by weak expression levels, especially when expression of more than one protein is required. Here, the authors overcome this limitation using deletion-mutant rabies viruses.
- Ian R. Wickersham
- , Heather A. Sullivan
- & H. Sebastian Seung
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Visualization and genetic modification of resident brain microglia using lentiviral vectors regulated by microRNA-9
Microglia are specialized immune cells in the brain. Here Åkerblom and colleagues use a microRNA-9-regulated lentiviral vector for the targeted genetic modification of microglia in the rodent brain, presenting a tool that may facilitate functional studies of resident microglia.
- Malin Åkerblom
- , Rohit Sachdeva
- & Johan Jakobsson
Leucine aminopeptidase1 controls egg deposition and hatchability in male Aedes aegypti mosquitoes