A chimeric infection program and epigenetic conflict underpin endogenous giant virus latency

Giant endogenous viral elements (GEVEs) inhabit the genomes of eukaryotic organisms, but the mechanisms behind their adaptation and reactivation despite host defenses are yet to be fully understood. In a study of the green alga Chlamydomonas reinhardtii and its latent giant virus, punuivirus, researchers have uncovered intriguing insights into this complex relationship.

The GEVEs in question display a chimeric genomic architecture, with latency genes residing within spliceosomal introns and bearing 6-methyladenine marks, reminiscent of host transcriptional regulation patterns. Conversely, the virulence genes are predominantly governed by a conserved viral promoter. Utilizing single-cell RNA sequencing, the team discovered that around 70% of the cells express viral transcripts, but only a fraction of them transition to producing virulence proteins, effectively silencing host transcription.

Intriguingly, the intact GEVE remains impervious to host-mediated 5-methylcytosine (5mC) silencing, while a naturally occurring deletion variant is linked to extensive 5mC buildup across the GEVE and other regions of the host genome. The deletion region houses a highly expressed ten-eleven translocation dioxygenase (TET), which plays a pivotal role in removing 5mC marks, thereby preserving the virus in a transcriptionally permissive latent state.

These findings offer fresh perspectives on the molecular underpinnings of the intricate dance between host and virus in the context of giant virus-alga coexistence.