In Situ Sustained Macrophage-Targeted Nanomicelle-Hydrogel Microspheres for Inhibiting Osteoarthritis.

LSH1 is a novel lytic siphovirus isolated, together with its host in the genus Alishewanella, from the surface microlayer of a brackish tidal reservoir in South Korea and characterized with respect to growth properties, genome sequence, gene annotation, mass spectrometry, and electron microscopy. Sequence analysis shows that LSH1 shares only distant similarity to other cultured phages, although a closer metagenomic neighborhood can be defined. LSH1 represents the first isolate from a large, previously unsampled family-level sector of the viral tree. Transmission electron microscopy revealed a tail end distinct from the best structurally characterized siphoviral prototypes and similar in appearance to Salmonella phage Jersey, the prototype of a large structurally uncharacterized group named Guernseyvirinae. Therefore, Jersey was included in the comparative analysis with LSH1. A combination of hidden Markov model comparisons and AlphaFold reconstruction was used to clarify the structural relationships of these phages. Both have structural homologs of portions of the canonical bacteriophage lambda tail hub but lack the lambda components associated with receptor recognition linked to ejection triggering in that system. The LSH1 and Jersey tail hubs are of different sequence lineages, but each represents a relatively minimalistic version of the siphoviral tail hub, with distinct candidates for the structural location of their antireceptors. This study explores the capability of AlphaFold to rapidly augment the relatively few structurally characterized phages with models for diverse variants, fleshing out how much variation there is and perhaps leading to a better treatment of how this variation is evolving.