Dengue virus is an important emerging pathogen, but so far there is no vaccine effective for all serotypes. Screaton and colleagues identify a class of broadly reactive human antibodies focused on an epitope that bridges two virion subunits. Dengue is a rapidly emerging, mosquito-borne viral infection, with an estimated 400 million infections occurring annually. To gain insight into dengue immunity, we characterized 145 human monoclonal antibodies (mAbs) and identified a previously unknown epitope, the envelope dimer epitope (EDE), that bridges two envelope protein subunits that make up the 90 repeating dimers on the mature virion. The mAbs to EDE were broadly reactive across the dengue serocomplex and fully neutralized virus produced in either insect cells or primary human cells, with 50% neutralization in the low picomolar range. Our results provide a path to a subunit vaccine against dengue virus and have implications for the design and monitoring of future vaccine trials in which the induction of antibody to the EDE should be prioritized.

The human cerebral cortex possesses distinct structural and functional features that are not found in the lower species traditionally used to model brain development and disease. Accordingly, considerable attention has been placed on the development of methods to direct pluripotent stem cells to form human brain-like structures termed organoids. However, many organoid differentiation protocols are inefficient and display marked variability in their ability to recapitulate the three-dimensional architecture and course of neurogenesis in the developing human brain. Here, we describe optimized organoid culture methods that efficiently and reliably produce cortical and basal ganglia structures similar to those in the human fetal brain in vivo. Neurons within the organoids are functional and exhibit network-like activities. We further demonstrate the utility of this organoid system for modeling the teratogenic effects of Zika virus on the developing brain and identifying more susceptibility receptors and therapeutic compounds that can mitigate its destructive actions.

A high-resolution structure of the bacteriophage MS2 sheds light on the structure of the genome and how the genome is delivered into a bacterium. Hong Zhou and colleagues provide the first description of genome–capsid interactions in a spherical single-stranded RNA (ssRNA) virus, using the bacteriophage MS2 as a model. Unlike double-stranded DNA viruses that pump their genome into a preformed capsid, ssRNA viruses co-assemble their capsid with their genome. Here the authors determine the MS2 structure at 3.6 Å resolution and are able to trace around 80% of the backbone of the viral genome, identifying regions that react with the maturation protein and providing insights into the ssRNA capsid co-assembly process. Packaging of the genome into a protein capsid and its subsequent delivery into a host cell are two fundamental processes in the life cycle of a virus. Unlike double-stranded DNA viruses, which pump their genome into a preformed capsid1,2,3, single-stranded RNA (ssRNA) viruses, such as bacteriophage MS2, co-assemble their capsid with the genome4,5,6,7; however, the structural basis of this co-assembly is poorly understood. MS2 infects Escherichia coli via the host ‘sex pilus’ (F-pilus)8; it was the first fully sequenced organism9 and is a model system for studies of translational gene regulation10,11, RNA–protein interactions12,13,14, and RNA virus assembly15,16,17. Its positive-sense ssRNA genome of 3,569 bases is enclosed in a capsid with one maturation protein monomer and 89 coat protein dimers arranged in a T = 3 icosahedral lattice18,19. The maturation protein is responsible for attaching the virus to an F-pilus and delivering the viral genome into the host during infection8, but how the genome is organized and delivered is not known. Here we describe the MS2 structure at 3.6 Å resolution, determined by electron-counting cryo-electron microscopy (cryoEM) and asymmetric reconstruction. We traced approximately 80% of the backbone of the viral genome, built atomic models for 16 RNA stem–loops, and identified three conserved motifs of RNA–coat protein interactions among 15 of these stem–loops with diverse sequences. The stem–loop at the 3′ end of the genome interacts extensively with the maturation protein, which, with just a six-helix bundle and a six-stranded β-sheet, forms a genome-delivery apparatus and joins 89 coat protein dimers to form a capsid. This atomic description of genome–capsid interactions in a spherical ssRNA virus provides insight into genome delivery via the host sex pilus and mechanisms underlying ssRNA–capsid co-assembly, and inspires speculation about the links between nucleoprotein complexes and the origins of viruses.

Focusing in on herpesvirus: The herpesvirus family includes herpes simplex virus type 1 (HSV-1), which causes cold sores, and type 2 (HSV-2), which causes genital herpes. Herpesviruses comprise a large DNA genome enclosed in a large and complex protein cage called a capsid (see the Perspective by Heldwein). Dai and Zhou used electron microscopy to determine a high-resolution structure of the HSV-1 capsid bound to the tegument proteins that occupy the space between the capsid and the nuclear envelope. The structure suggests how these components may play a role in viral transport. Yuan et al. describe a higher-resolution structure of an HSV-2 capsid, providing insight into how the shell assembles and is stabilized. Science , this issue p. eaao7298 , p. eaao7283 ; see also p. 34