# The infection cycle of the haloarchaeal virus HFTV1 is tightly regulated and strongly inhibits motility of its host

## TL;DR

This study explores how the virus HFTV1 infects Haloferax gibbonsii, revealing unique gene regulation strategies and how it inhibits host movement to focus on virus production.

## Contribution

The study reveals novel regulatory mechanisms in HFTV1, including antisense RNAs and intragenic elements, which differ from bacterial virus models.

## Key findings

- HFTV1 shows tight temporal regulation of viral transcripts and differential expression of gene clusters.
- Antisense RNAs and intragenic elements play a key role in regulating late-expressed viral genes.
- Host motility genes are strongly downregulated in infected cells, confirmed by swimming assays.

## Abstract

Although viruses have been shown to infect all domains of life, our understanding of the genetic program behind the exploitation of host resources to produce progeny virions is thus far limited to several bacterial viruses. Therefore, to elucidate the transcriptome of euryarchaeal viruses and their hosts, we employed RNAseq analysis of samples taken at different time points from Haloferax gibbonsii LR2-5 cultures infected with the lytic model virus Haloferax tailed virus 1 (HFTV1). While following the transcription of viral genes throughout the infective life cycle, we observed a tight temporal regulation of viral transcripts and differential expression from within viral gene clusters. Furthermore, antisense RNAs (asRNAs) appear to play an important role in support of the timing of late-expressed viral genes. Therefore, with many differentially expressed transcripts, including intragenic transcripts and asRNAs, the regulatory machinery employed by HFTV1 contrasts with that of viral model systems (based on phages), in which antitermination and/or alternative polymerases (seemingly lacking in HFTV1) are more widespread. When examining differentially expressed host genes, we observed a strong downregulation of genes involved in motility, such as those encoding the archaellum and chemotaxis machinery, which was confirmed by swimming assays of HFTV1 infected cells. This might be a strategy of the virus to redirect energy flowing into movement toward the production of virions. In conclusion, this work provides a stepping stone for further exploration of the intriguing strategies of viral transcriptional regulation throughout their infection cycle across the domains of life.

Viruses infect members of all three domains of life, including Archaea. Euryarchaea are widespread microorganisms found in various environments, such as the human gut and solar salterns. Due to the exceptional availability of cell biology and genetic tools for some salt-loving archaea, they serve as a model system from which insights can be extrapolated. Insights into the regulation of viral infections are of particular importance, especially since HFTV1 has been adopted as a model virus by the archaeal viral community. We found that, while harboring parallels with bacterial viruses, such as tight temporal regulation, HFTV1 harbors an impressive number of differentially expressed transcriptional units. Furthermore, antisense RNAs and intragenic regulatory elements seem to play a much more prominent role in HFTV1 gene expression. Thus, this work challenges current models and provides valuable new insights into the gene regulation of viral infection of archaea, which mark similarities and differences with viruses from other domains of life.