Vertical transmission in Caenorhabditis nematodes of RNA molecules encoding a viral RNA-dependent RNA polymerase

Aurélien Richaud; Lise Frézal; Stephen Tahan; Hongbing Jiang; Joshua A. Blatter; Guoyan Zhao; Taniya Kaur; David Wang; Marie-Anne Félix

doi:10.1073/pnas.1903903116

New Research In

Edited by Anne M. Villeneuve, Stanford University, Stanford, CA, and approved October 14, 2019 (received for review March 6, 2019)

Significance

In organisms composed of a single cell, RNAs of viral origin may be transmitted to daughter cells at cell division without passing through an extracellular virion stage. These RNAs usually encode an RNA-dependent RNA polymerase that enables their replication. For some of these agents, such as Narnaviruses, no capsid protein is expressed, and thus, they are called capsidless viruses. Here, we identify putative capsidless viral RNAs in animals, in nematodes closely related to the model organism Caenorhabditis elegans. We show that these RNAs are transmitted vertically through the host germline. Our work provides evidence that animal cells harbor capsidless viruses.

Abstract

Here, we report on the discovery in Caenorhabditis nematodes of multiple vertically transmitted RNAs coding for putative RNA-dependent RNA polymerases. Their sequences share similarity to distinct RNA viruses, including bunyaviruses, narnaviruses, and sobemoviruses. The sequences are present exclusively as RNA and are not found in DNA form. The RNAs persist in progeny after bleach treatment of adult animals, indicating vertical transmission of the RNAs. We tested one of the infected strains for transmission to an uninfected strain and found that mating of infected animals with uninfected animals resulted in infected progeny. By in situ hybridization, we detected several of these RNAs in the cytoplasm of the male and female germline of the nematode host. The Caenorhabditis hosts were found defective in degrading exogenous double-stranded RNAs, which may explain retention of viral-like RNAs. Strikingly, one strain, QG551, harbored three distinct virus-like RNA elements. Specific patterns of small RNAs complementary to the different viral-like RNAs were observed, suggesting that the different RNAs are differentially recognized by the RNA interference (RNAi) machinery. While vertical transmission of viruses in the family Narnaviridae, which are known as capsidless viruses, has been described in fungi, these observations provide evidence that multicellular animal cells harbor similar viruses.

Footnotes

↵¹To whom correspondence may be addressed. Email: davewang{at}wustl.edu or felix{at}biologie.ens.fr.

Author contributions: D.W. and M.-A.F. designed research; A.R., L.F., S.T., and H.J. performed research; T.K. contributed new reagents/analytic tools; J.A.B., G.Z., D.W., and M.-A.F. analyzed data; and A.R., D.W., and M.-A.F. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
Data deposition: The sequences reported in this paper have been deposited in the NCBI Sequence Read Archive (accession nos. SRR8869242–SRR8869245 [BioProject PRJNA531652] for initial RNA sequencing, SRR9206839–SRR9206841 [BioProject PRJNA531652] for DNA sequencing, and SRX6374058–SRX6374060 [BioProject PRJNA551618] for small RNA sequencing). The viral-like RNA contigs reported in this paper have been deposited in the NCBI Nucleotide (accession no. KM580531 for the Caenorhabditis brenneri JU1396 bunya-like RNA and MN272066–MN272070 for the other viral-like RNAs; Table 1).
This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.1903903116/-/DCSupplemental.