Expanding the size limit of RNA viruses: Evidence of a novel divergent nidovirus in California sea hare, with a ~35.9 kb virus genome

Debat, Humberto J

While RNA viruses thrive with massive structural and functional diversity, their genomes size variation is particularly low, ranging only from ~2-to-33 kb. Here, I present the characterization of RNA sequences corresponding to the first virus associated with Aplysia californica. Genome structure and domain architecture suggest that the identified virus is a novel member of Nidovirales. The proposed aplysia californica nido-like virus (AcNV), with a genome sequence of ca.35,906 nt, represents the longest ever recorded RNA virus yet. Phylogenetic insights indicate that AcNV clusters in a major phylloclade of unclassified invertebrate nidoviruses, Roniviridae, and Mesoniviridae. Basal branching in this emerging cluster could indicate that AcNV is a member of a novel divergent clade within Nidovirales. Further, virus RNA detection in multiple independent studies suggests that AcNV is neurotropic with a broad cell/tissue/organ tropism, supported by AcNV occurrence in diverse organs, including the first detection of a Nidovirales in single specific neurons. Highlights -RNA virus genomes reported in the literature are limited at ca. 33.4 kb -A novel nidovirus was identified in the gastropod mollusk Aplysia californica -The aplysia californica nido-like virus (AcNV) presents a 35.9 kb RNA genome -AcNV has a broad tropism, is enriched in the CNS, and accumulates in neurons -The unique features of A. californica enables single-neuron virus dynamics of AcNV