Massive Activation of Archaeal Defense Genes during Viral Infection

Abstract

dArchaeal viruses display unusually high genetic and morphological diversity. Studies of these viruses proved to be instrumental for the expansion of knowledge on viral diversity and evolution. The Sulfolobus islandicus rod-shaped virus 2 (SIRV2) is a model to study virus-host interactions in Archaea. It is a lytic virus that exploits a unique egress mechanism based on the formation of remarkable pyramidal structures on the host cell envelope. Using whole-transcriptome sequencing, we present here a global map defining host and viral gene expression during the infection cycle of SIRV2 in its hyperthermophilic host S. islandicus LAL14/1. This information was used, in combination with a yeast two-hybrid analysis of SIRV2 protein interactions, to advance current understanding of viral gene functions. As a consequence of SIRV2 infection, transcription of more than one-third of S. islandicus genes was differentially regulated. While expression of genes involved in cell division decreased, those genes playing a role in antiviral defense were activated on a large scale. Expression of genes belonging to toxin-antitoxin and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems was specifically pronounced. The observed different degree of activation of various CRISPR-Cas systems highlights the specialized functions they perform. The information on individual gene expression and activation of antiviral defense systems is expected to aid future studies aimed at detailed understanding of the functions and interplay of these systems in vivo.

Knowledge-based discovery for designing CRISPR-CAS systems against invading mobilomes in thermophiles

“…Cas1, cas3, and cas4 proteins are homologous to a DNA repair protein, a helicase, and recB exonuclease, respectively. The predicted proteins of this study are directly contributed in DNA a repair and recombination mechanism, which was agreed to earlier annotation (Brügger et al 2002;Sasaki et al 2004;Godde and Bickerton 2006;Weinberger et al 2012;Quax et al 2013).…”

“…The common structural characteristics of CRISPR loci are: (1) multiple short direct repeats (2) non-repetitive spacer sequences between the repeats of similar size (3) a common leader sequence of a few hundred base pairs harboring multiple CRISPR loci and (4) accompanied by cas gene families. The principal products of the CRISPR loci are comprised primarily of invader-targeting sequences that are likely the guides for effector complexes of pRNAi system (Hale et al 2008;Quax et al 2013;Cooper and Overstreet 2014). CRISPR-CAS systems confer viral resistance in these genomes remain hypothetical and undefined.…”

“…Among 25 gene families in the CAS system, eight gene families (cas1, cas2, cas4, cas6, cas7) have reported for the nuclease activity, nine families (cas5) for Repeat-Associated Mysterious Proteins (RAMP) and two families (cas3) for DNA/RNA polymerase/helicase activity (Makarova et al 2006;Quax et al 2013;Vestergaard et al 2014). However, the functions of several other cas gene families remain obscure.…”

Structure and assembly mechanism of virus-associated pyramids

“…One possibility is that the two proteins have different capabilities to bind interaction partners. For example, host-encoded ESCRT (Endosomal Sorting Complex Required for Transport) homologues are involved in the STIV1 infection cycle, but not in that of SIRV2 (Quax et al 2013;Snyder et al 2013b;Daum et al 2014). The only other viruses to have homologues of the PVAP protein, besides STIV1 and SIRV2, are the archaeal viruses of the Rudiviridae family (Quax et al 2010).…”

Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system

“…To limit fitness costs, some CRISPR-Cas systems are induced upon infection (11)(12)(13). Other environmental cues regulate CRISPR-Cas.…”