Decoding the Enigma: First Look at a Chapparvovirus Capsid Reveals a New Chapter in Viral Evolution

Parvoviruses, a vast and diverse family of single-stranded DNA (ssDNA) viruses, are known for infecting a wide range of animals, from humans and pets to livestock and invertebrates. Among them, chapparvoviruses (ChPVs) stand out as a divergent lineage within the Parvoviridae family, having evolved to infect vertebrate animals independently from the well-studied Parvovirinae subfamily. Despite their prevalence in environmental samples and their identified pathogenic nature in various hosts, including rodents and primates, their structural characterization has proven remarkably challenging.

            However, recent research by Jason Kaelber at the Rutgers Institute for Quantitative Biomedicine marks a breakthrough: the first structural analysis of a ChPV4. The research focuses on Syngnathus scovelli chapparvovirus (SsChPV), a pathogen of the gulf pipefish, offering a glimpse into this enigmatic lineage and providing a fresh perspective on parvovirus structural biology.

            The research leveraged cryo-electron microscopy (cryo-EM) to resolve the SsChPV capsid structure at an impressive 2.93 Å resolution, a significant technical achievement given the difficulties in obtaining intact ChPV particles. The work challenges several established concepts about parvovirus architecture and function.  Unlike many other characterized parvoviruses that form mosaic capsids from multiple isoforms of their structural proteins, the SsChPV capsid is assembled from 60 copies of a single structural protein. This simplicity in its composition is rare among parvoviruses.

            A defining characteristic of almost all parvoviruses thus far has been the presence of long, flexible N-terminal structural protein domains. These domains are crucial for processes like intracellular trafficking, endosomal egress, and externalizing enzymatic regions or signaling peptides through the fivefold channel, a characteristic pore-like opening found at the fivefold symmetry axis of parvovirus capsids. However, the research reveals that ChPVs, including SsChPV, completely lack any such N-terminal sequences. This trait appears to be conserved throughout the ChPV lineage. Consequentially, the absence of these N-terminal domains in SsChPV has led to the degradation of their fivefold channel, which is typically the site for N-terminus externalization. This makes the SsChPV fivefold pore significantly different from most parvoviruses, although similar reduced channels have been observed in certain invertebrate-infecting Densovirinae and human parvovirus B19.

            The SsChPV capsid lacks the typical stability and resilience seen in other parvovirus capsids. This is attributed to the absence of interacting β-strands at its twofold symmetry axis, which are usually vital for structural support. This results in a significantly weaker two-fold interface compared to other parvoviruses. The low stability of these particles may explain why ChPVs have been so difficult to observe or isolate in vivo, and it suggests that their infectious pathway might involve quick particle disassembly, for example, during uncoating.

            Instead of the common "β-annulus pore" found at the threefold axis in some denso- and hamaparvoviruses, SsChPV evolved a threefold-related depression of α-helices. While structurally different from the β-annulus, this opening may serve a similar purpose: facilitating monomer oligomerization during assembly, potentially by guiding the formation of trimers as the basic building blocks of the 60-subunit capsid. This analogous function, despite differing evolutionary origins, implies convergent assembly mechanisms across distinct parvovirus lineages.

            ChPVs not only represent an evolutionarily divergent parvovirus lineage but also appear to possess a fundamentally distinct viral life cycle from other members of the Parvoviridae family. This pioneering structural work on SsChPV provides crucial foundational knowledge, paving the way for deeper understanding of this widespread and pathogenic group of viruses and their unique strategies for infection and survival.  

Penzes JJ, Kaelber JT. Capsid Structure of the Fish Pathogen Syngnathus Scovelli Chapparvovirus Offers a New Perspective on Parvovirus Structural Biology. Viruses. 2025 May 6;17(5):679. doi: 10.3390/v17050679. PMID: 40431691; PMCID: PMC12115719. https://www.mdpi.com/1999-4915/17/5/679