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Giant viruses are large DNA viruses with capsid diameters up to 500 nm. Given technical challenges only few high-resolution structures of viral capsids exist. Here, Shao et al. provide a nearatomic structure of giant virus PBCV-1 capsid and resolve the previously unknown asymmetric capsid components. The local capsid microenvironments created by these components provide insights into the mechanism of capsid assembly of giant viruses.

Here, the authors present the cryo-EM structures of two archaeal, halophilic, internal membrane-containing icosahedral viruses at 3.7 and 3.8 Å resolution, providing insights into the assembly process of these and related PRD1-adeno lineage viruses.

In the adrenal cortex, cholesterol used for steroid production is stored in lipid droplets. The authors demonstrate here the importance of the transcription factor HHEX in maintaining glucocorticoid levels and protecting lipid droplets from androgen-induced lipid depletion.

Here, the authors present the cryo-EM structure of the archaeal virus SH1 at 3.8 Å resolution and show how the major capsid proteins assemble into hetero-hexamers, providing insights into the assembly process of this and related PRD1-adeno lineage viruses.

Viral infection is a common risk for immune-compromised individuals, particularly pediatric patients receiving hematopoietic stem cell transplants. Here the authors report a phase II trial testing adoptive transfer of third party, virus-specific T cells on the feasibility, safety, clinical responses, as well as homeostasis of antiviral immunity in the recipients.

Using viral capsid architectures as template for design, higher triangulation number nanocages that require symmetry breaking offer potential advances in targeted delivery and antigen-displaying vaccines.

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.

Leveraging bioinformatics, proteomics, and cryogenic electron microscopy, this study deciphers the architecture and design principles of the therapeutic Pseudomonas phage Pa193.

Targeting a non-natural micropeptide ‘killswitch’ to several biomolecular condensates altered condensate compositions and revealed condensate functions in human cells

Cryogenic electron tomography analysis of Chikungunya virus particle assembly reveals 12 intermediate structural stages during virus assembly/budding at the plasma membrane and shows that non-icosahedral nucleocapsid proteins serve as scaffold to induce icosahedral assembly of the glycoprotein spike lattice. Structural analysis also shows that budding-inhibiting antibodies act by interfering with lateral spike interactions.

Pule and colleagues identify the TCR β-chain constant region as a new target for chimeric antigen receptor (CAR) T cells in treatment of T cell cancers while potentially preserving a healthy T cell repertoire. They demonstrate that anti-TCRB1 CAR T cells eliminate cancerous TCRB1⁺ T cells while sparing nearly one-third of normal TCRB2⁺ T cells.

The Epstein-Barr virus (EBV) is a dangerous human pathogen responsible for mononucleosis and several types of cancers. Here the authors describe a high-resolution atomic structure of the EBV portal, which serves as the entrance and exit pore for the viral genome and is a potential pharmacological target for the development of antivirals.

Off-the-shelf CAR T cells avoid immune rejection in mouse models of allogeneic cancer cell therapy.

A single-cell ex vivo screening of repurposable drugs in glioblastoma and machine learning of drug–target networks show that anti-tumor neuroactive drugs converge on the AP-1/BTG pathway, based on which prediction models and experimental in vivo and in silico validation identify the anti-depressant vortioxetine as a potential therapeutic agent.

Some viral proteins involved in interaction with the host cell surface adopt a very rigid and stable triple–β-helix fold. In order to attain this complex fold, these proteins contain an intramolecular chaperone domain that is auto-cleaved after assembly. Now structural work on two such chaperone domains indicates how they can promote correct folding of the β-helices.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

There are many open questions about biogeochemical function in peatlands. Here, the authors investigate the nitrogen cycle of tropical peatlands, finding that a surprisingly high fraction of nitrous oxide production is abiotic and that denitrification is a coupled abiotic-biotic process.

A key challenge in gene therapy is vector targeting to specific cells, while avoiding effects on other tissues. Several strategies have been developed recently to enable targeting of the main viral vectors, moving them a step closer to clinical use.

The full extent of the genetic basis for hearing impairment is unknown. Here, as part of the International Mouse Phenotyping Consortium, the authors perform a hearing loss screen in 3006 mouse knockout strains and identify 52 new candidate genes for genetic hearing loss.

Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium.

The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.

Egress of herpesviruses requires that viral capsids containing the viral DNA travel from the nucleus to the cell surface, traversing nuclear and cytoplasmic membranes. Johnson and Baines describe how viral proteins remodel cellular membranes in order to escape host cells.

Magnetospheres of exoplanets are vast, tenuous and hard to detect. Deep blue-shifted absorption lines observed in the extended region around HAT-P-11 b may provide evidence for a magnetosphere and magnetotail.

Patient-derived neuronal models highlight the importance of mitochondrial dysfunction during prolonged action potential firing in the context of the rare metabolic disease methylmalonic aciduria.

Felix Beuschlein, Martin Reincke and colleagues identify recurrent somatic mutations in ATP1A1 and ATP2B3 in aldosterone-producing adenomas with wild-type KCNJ5. The ATP1A1 and ATP2B3 mutations alter conserved residues and lead to impaired sodium, potassium and calcium ion homeostasis.

The International Mouse Phenotyping Consortium reports the generation of new mouse mutant strains for more than 5,000 genes, including 2,850 novel null, 2,987 novel conditional-ready and 4,433 novel reporter alleles.

Bret Moore et al. from the International Mouse Phenotyping Consortium report the identification of 347 mouse genes that influence ocular phenotypes when knocked out. 75% of the identified genes have not previously been associated with any ocular pathology.