Virus-host interactions mediated by pea enation mosaic virus 2 biomolecular condensates
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Abstract
The concept of phase separation applied to biological systems has been rapidly building momentum and interest. Phase separation is the conversion of a single-phase solution into two distinct phases: a dilute phase and a concentrated droplet phase. When applied to cells, the term droplet refers to membraneless organelles or condensates that concentrate biomolecules like proteins and RNA. Viruses can interfere with host condensates, like the nucleolus or stress granules, as well as generate condensates to facilitate viral processes. Our research suggests that electrostatic interactions in the intrinsically disordered region of p26, a movement protein encoded by the +sense RNA plant virus Pea enation mosaic virus 2 (PEMV2), drive p26 phase separation to form viral condensates. We demonstrate co-localization of p26 with host proteins, specifically fibrillarin and G3BP1, into condensates during virus infection and subsequently illustrate the importance of G3BP1 phase separation in the plant anti-viral response. These findings outline a key role for p26 phase separation in the coordination of virus-host interactions, viral ribonucleoprotein (vRNP) formation, and systemic virus movement. This work explores how host- and virus-induced phase separation impacts virus-host interactions to promote or restrict a virus infection.Viral condensate research has predominantly centered around the formation of membraneless replication factories by negative sense viruses. However, the function and composition of cytoplasmic condensates formed by positive sense RNA viruses, which utilize membrane-associated replication factories, has been largely uninvestigated. Mass spectrometry revealed that p26 condensates were enriched with ribosomal proteins and fibrillarin, a host rRNA methyltransferase hijacked by PEMV2 to support virus movement. Our data shows that p26 expression represses global translation >40% in plants. In corroboration, polysome profiling exposed significant defects in monosome formation for p26-overexpression and virus-infected samples, whereas infection with a mutant virus lacking p26 partially rescued monosome formation.
Our findings suggest that p26 binds rRNA with a high affinity, yet there was no significant alteration in rRNA abundance, processing, or 2’-O-methylation. Therefore, we propose that p26-mediated sequestration of fibrillarin, mRNA, rRNA, and ribosomal proteins into condensates may serve as a switch to repress translation in favor of virus trafficking, a process incompatible with active translation.
Table of Contents
An introduction to viruses and phase separation -- Phase separation of a plant virus movement protein and cellular factors support virus-host interactions -- Viral condensates formed by pea enation mosaic virus 2 sequester ribosomal components and suppress translation -- Conclusion
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Ph.D. (Doctor of Philosophy)