ORF4 of the Temperate Archaeal Virus SNJ1 Governs the Lysis-Lysogeny Switch and Superinfection Immunity

Abstract

Recent environmental and metagenomic studies have considerably increased the repertoire of archaeal viruses and suggested that they play important roles in nutrient cycling in the biosphere. However, very little is known about how they regulate their life cycles and interact with their hosts. Here, we report that the life cycle of the temperate haloarchaeal virus SNJ1 is controlled by the product ORF4, a small protein belonging to the antitoxin MazE superfamily. We show that ORF4 controls the lysis-lysogeny switch of SNJ1 and mediates superinfection immunity by repression of genomic DNA replication of the superinfecting viruses. Bioinformatic analysis shows that ORF4 is highly conserved in two SNJ1-like proviruses, suggesting that the mechanisms for lysis-lysogeny switch and superinfection immunity are conserved in this group of viruses. As lysis-lysogeny switch and superinfection immunity of archaeal viruses are poorly studied, we suggest that SNJ1 could serve as a model system to study these processes. IMPORTANCE Archaeal viruses are important parts of the virosphere. Understanding how they regulate their life cycles and interact with host cells provide crucial insights into their biological functions and the evolutionary histories of viruses. However, mechanistic studies of the life cycle of archaeal viruses are scarce due to a lack of genetic tools and demanding cultivation conditions. Here, we discover that the temperate haloarchaeal virus SNJ1, which infects Natrinema sp. J7, employs a lysis-lysogeny switch and establishes superinfection immunity like bacteriophages. We show that its ORF4 is critical for both processes and acts as a repressor of the replication of SNJ1.These results establish ORF4 as a master regulator of SNJ1 life cycle and provides novel insights on the regulation of life cycles by temperate archaeal viruses and on their interactions with host cells.

A highly conserved and globally prevalent cryptic plasmid is among the most numerous mobile genetic elements in the human gut

“…We assumed that if priority effects are driving persistence of a single version of pBI143, the first version that enters the infant gut environment should be maintained over time. Indeed, many phage populations are influenced by priority effects where the presence of one phage provides a competitive advantage to the host 88 or host immunity to infection with similar phages [89][90][91] . In our data, we found no instances where pBI143 acquired from the mother was fully replaced in the infant during and up to the first year of life (Supplementary Fig.…”

ICTV Virus Taxonomy Profile: Simuloviridae 2023

“…The Saline Natrinema sp. J7‐1 virus 1-encoded ORF4 is a transcriptional regulator belonging to the MazE superfamily and controls the lysis–lysogeny switch [3]. The virus is triggered to undergo the lytic life cycle upon treatment with the DNA-damaging agent mitomycin C. Homologues of Saline Natrinema sp.…”

“…2). Simuloviruses share 17-21 homologous ORFs including replication, regulation and virion structure-related genes; these gene modules are generally collinear among simuloviruses [3].…”

Metagenomic analysis reveals unexplored diversity of archaeal virome in the human gut

“…In particular, we observed that 10 genomes infecting Methanobrevibacter_A smithii or M. olleyae encoded proteins belonging to the antitoxin MazE superfamily. The toxin-antitoxin system on a temperate virus acts as an addiction system, preventing the host from curing itself from the provirus 31 . Accordingly, the presence of the antitoxin MazE protein on the HGAVD archaeal viruses might highlight an arms race between the gut archaea and their viruses.…”