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

Bacterial flagella are known for facilitating motility to support nutrient acquisition and predator evasion, but can also serve as receptors for phages. Here, we characterize a dual role of flagella during infection of Yersinia enterocolitica by phage X1: functioning as a conduit for phage DNA entry and as a trigger for bacterial defense. X1 employs a “contraction-driven” mechanism, using its contractile tail to inject DNA into Yersinia flagella. Unlike other characterized flagellotropic phages that rely exclusively on flagella or less efficiently on secondary surface receptors, X1 can infect cells via lipopolysaccharides with even higher efficiency. Furthermore, certain Yersinia strains can detect X1 invasion and activate a flagellum-dependent toxin–antitoxin (Flag-TA) system, which requires the flagellar motor stator proteins MotAB to activate the abortive infection response. Our findings reveal a novel phage infection strategy and uncover a new bacterial defense that are both based on the flagellar machinery.

• Deletion of residues 156–157 warps the neighboring beta-sheet and leads NTD and RBD to shift. • T859N stabilizes the packing of the 630 loop motif to make RBD standing transition more difficult. • The overall structures of the closed state S complex from different variants resemble each other. • Mutations in FPPR may affect the overall structure of the trimeric spike protein.

The arms race between phages and bacteria is dynamic and ongoing, with both continuously acquiring new strategies to outcompete each other during co-evolution. Here, we report bacteriophage T4 exonuclease DexA and an uncharacterized Escherichia coli exonuclease as a rare pair of attack and defense duo arising from the same mechanism. DexA, highly conserved among phages, has two well-characterized biological roles: host DNA scavenging and intron homing. Unmodified DNA is the substrate during host DNA scavenging, whereas cleavage of 5hmC (5-hydroxymethylcytosine)-modified phage DNA is required for intron homing. We reveal a temperature-driven quaternary fold switch between DexA dimer and tetramer that facilitates cleavage of distinct DNA forms, namely 5hmC-modified phage DNA and unmodified host DNA. As a countermeasure, bacteria produce DexA variants for defense against phage that only targets 5hmC-modified DNA. Thus, both phages and bacteria compete using HmC-Recognizing EXonuclease strategies (designated as HREX).

Nonstructural protein 1 (Nsp1) is a key virulence factor of coronaviruses, and its stable binding to the 40S ribosomal mRNA entry channel facilitates multiple functions, including suppression of host immune responses and degradation of host mRNA. To understand the structural basis of the conserved protein across viral lineages, we determined the cryo-EM structures of Nsp1–40S complexes of four coronaviruses from wild animals. Our results show that all Nsp1 proteins engage the mRNA entry channel via their C-terminal domain (CTD), but do not fully restrict the rotational mobility of the 40S head, which retains ∼5° of movement and repositions the Nsp1 linker region. Comparative analysis revealed distinct patterns in the linker regions connecting the N- and CTDs. Sarbecovirus Nsp1 contains a longer linker, whereas the merbecovirus Nsp1 adopts a shorter linker that navigates structural constraints more readily. Functionally, we find that linker length correlates with translation inhibition efficiency, suggesting a structural tuning mechanism. Additionally, variations in linker and helix 1 of the CTD among different lineages may serve as molecular markers for viral classification. Together, our results provide a comparative structural framework for understanding how coronavirus Nsp1 proteins modulate host translation and reflect evolutionary adaptations in ribosome engagement.