Newmark, P. A. | Search bioRxiv

bioRxiv2018

A novel rotifer-derived alkaloid paralyzes schistosome larvae and prevents infection

Schistosomes are parasitic flatworms that infect over 200 million people, causing the neglected tropical disease, schistosomiasis. A single drug, praziquantel, is used to treat schistosome infection. Limitations in mass drug administration programs and the emergence of schistosomiasis in non-tropical areas indicate the need for new strategies to prevent infection. It has been known for several decades that rotifers colonizing the schistosomes snail intermediate host produce a water-soluble factor that paralyzes cercariae, the life-cycle stage infecting humans. In spite of its potential for preventing infection, the nature of this factor has remained obscure. Here, we report the purification and chemical characterization of Schistosome Paralysis Factor (SPF), a novel tetracyclic alkaloid produced by the rotifer Rotaria rotatoria. We show that this compound paralyzes schistosome cercariae and prevents infection, and does so more effectively than analogous compounds. This molecule provides new directions for understanding cercariae motility and new strategies for preventing schistosome infection.

biochemistry↗

bioRxiv2018

A planarian nidovirus expands the limits of RNA genome size

RNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication (albeit within a permissive environment). A 33.5-kb nidovirus has been considered close to the upper size limit for such entities; conversely, the minimal cellular DNA genome is ~200 kb. This large difference presents a daunting gap for the transition from primordial RNP to contemporary DNA-RNP-based life. Whether or not RNA viruses represent transitional steps on the road to DNA-based life, studies of larger RNA viruses advance our understanding of size constraints on RNP entities. For example, emergence of the largest previously known RNA genomes (20-34 kb in positive-stranded nidoviruses, including coronaviruses) is associated with a proofreading exoribonuclease encoded in the nidoviral open reading frame 1b (ORF1b). However, apparent constraints on the size of ORF1b, which encodes this and other key replicative enzymes, have been hypothesized to limit further expansion of viral RNA genomes. Here, we characterize a novel nidovirus (planarian secretory cell nidovirus; PSCNV) whose disproportionately large ORF1b-like region, and overall 41.1 kb genome, substantially extend the presumed limits on RNA genome size. This genome encodes a predicted 13,556-aa polyprotein in an unconventional single ORF, yet retains canonical nidoviral genome organization and expression, and key replicative domains. Our evolutionary analysis suggests that PSCNV diverged early from multi-ORF nidoviruses, and subsequently acquired additional genes, including those typical of large DNA viruses or hosts. PSCNVs greatly expanded genome, proteomic complexity, and unique features - impressive in themselves - attest to the likelihood of still-larger RNA genomes awaiting discovery.\n\nSignificance StatementRNA viruses are the only known RNA-protein (RNP) entities capable of autonomous replication. The upper genome size for such entities was assumed to be <35 kb; conversely, the minimal cellular DNA genome is ~200 kb. This large difference presents a daunting gap for the proposed evolution of contemporary DNA-RNP-based life from primordial RNP entities. Here, we describe a nidovirus from planarians, whose 41.1 kb genome is 23% larger than the largest known of RNA virus. The planarian secretory cell nidovirus has broken apparent constraints on the size of the genomic subregion that encodes core replication machinery, and has acquired genes not previously observed in RNA viruses. This virus challenges and advances our understanding of the limits to RNA genome size.

microbiology↗