Cryo-EM Structure of Siphophage Avs-1 Reveals a Conserved Virion Architecture with a Specialized Tripod-like Tail Tip for Host Recognition

Abstract

Bacteriophages are increasingly considered viable alternatives to antibiotics for controlling aquaculture pathogens, yet the structural basis of siphophage infection in aquatic bacteria remains largely unexplored. Here, we present the near-atomic-resolution cryo-electron microscopy structure of Avs-1, a siphophage infecting the freshwater aquaculture pathogen Aeromonas veronii. The capsid reconstruction at 2.98 Å and spike structure at 3.58 Å reveal a virion architecture broadly conserved among lambda-like siphophages, including an HK97-fold capsid, a canonical portal–neck complex, and a tail tube composed of approximately 26 stacked hexameric rings. However, the distal tail tip exhibits pronounced specialization, assembling into a C3-symmetric tripod-like core formed by the distal tail protein, hub protein, insertion protein, and the C-terminus of the tape measure protein. The trimeric spike protein gp43 extends from this platform and adopts a β-helical scaffold with a structurally divergent distal domain (D4), highlighting the structural diversity of phage tail-tip architectures. Together, these results reveal how a largely conserved virion framework is combined with a diversified distal tail apparatus, expanding the structural repertoire of characterized siphophages and providing a framework for investigating the molecular basis of phage–host interactions.