Identification of hidden N4-like viruses and their interactions with hosts
Kaiyang Zheng,
Yantao Liang,
David Paez-Espino,
Xiao Zou,
Chen Gao,
Hongbing Shao,
Yeong Yik Sung,
Wen Jye Mok,
Li Lian Wong,
Yu-Zhong Zhang,
Jiwei Tian,
Feng Chen,
Nianzhi Jiao,
Curtis A. Suttle,
Jianfeng He,
Andrew McMinn,
Min Wang
Affiliations
Kaiyang Zheng
Key Laboratory of Polar Oceanography and Global Ocean Change, Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Ocean University of China , Qingdao, China
Yantao Liang
Key Laboratory of Polar Oceanography and Global Ocean Change, Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Ocean University of China , Qingdao, China
David Paez-Espino
DOE Joint Genome Institute, Lawrence Berkeley National Laboratory , Berkeley, California, USA
Xiao Zou
Qingdao Central Hospital , Qingdao, China
Chen Gao
Key Laboratory of Polar Oceanography and Global Ocean Change, Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Ocean University of China , Qingdao, China
Hongbing Shao
Key Laboratory of Polar Oceanography and Global Ocean Change, Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Ocean University of China , Qingdao, China
Yeong Yik Sung
UMT-OUC Joint Centre for Marine Studies , Qingdao, China
Wen Jye Mok
UMT-OUC Joint Centre for Marine Studies , Qingdao, China
Li Lian Wong
UMT-OUC Joint Centre for Marine Studies , Qingdao, China
Yu-Zhong Zhang
Key Laboratory of Polar Oceanography and Global Ocean Change, Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Ocean University of China , Qingdao, China
Jiwei Tian
Key Laboratory of Physical Oceanography, Ministry of Education, Ocean University of China , Qingdao, China
Feng Chen
Institute of Marine and Environmental Technology, University of Maryland Center for Environmental Science , Baltimore, Maryland, USA
Nianzhi Jiao
State Key Laboratory of Marine Environmental Sciences, Institute of Marine Microbes and Ecospheres, Xiamen University , Xiamen, China
Curtis A. Suttle
Department of Earth, Ocean and Atmospheric Sciences, Institute for the Oceans and Fisheries, The University of British Columbia , Vancouver, British Columbia, Canada
Jianfeng He
SOA Key Laboratory for Polar Science, Polar Research Institute of China , Shanghai, China
Andrew McMinn
Key Laboratory of Polar Oceanography and Global Ocean Change, Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Ocean University of China , Qingdao, China
Min Wang
Key Laboratory of Polar Oceanography and Global Ocean Change, Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Institute of Evolution and Marine Biodiversity, Ocean University of China , Qingdao, China
ABSTRACT The N4-like viruses, which were recently assigned to the novel viral family Schitoviridae in 2021, belong to a podoviral-like viral lineage and possess conserved genomic characteristics and a unique replication mechanism. Despite their significance, our understanding of N4-like viruses is primarily based on viral isolates. To address this knowledge gap, this study has established a comprehensive N4-like viral data sets comprising 342 high-quality N4-like viruses/proviruses (144 viral isolates, 158 uncultured viruses, and 40 integrated N4-like proviruses). These viruses were classified into 97 subfamilies (89 of which are newly identified), 148 genera (100 of which are newly identified), and 253 species (177 of which are newly identified). The study reveals that N4-like viruses inhibit the polar region, oligotrophic open oceans, and the human gut, where they infect various bacterial lineages, such as Alpha/Beta/Gamma/Epsilon-proteobacteria in the Proteobacteria phylum. Although N4-like viral endogenization appears to be prevalent in Proteobacteria, it has also been observed in Firmicutes. Additionally, the phylogenetic analysis has identified evolutionary divergence within the hallmark genes of N4-like viruses, indicating a complex origin of the different conserved parts of viral genomes. Moreover, 1,101 putative auxiliary metabolic genes (AMGs) were identified in the N4-like viral pan-proteome, which mainly participate in nucleotide and cofactor/vitamin metabolisms. Of these AMGs, 27 were found to be associated with virulence, suggesting their potential involvement in the spread of bacterial pathogenicity. Importance The findings of this study are significant, as N4-like viruses represent a unique viral lineage with a distinct replication mechanism and a conserved core genome. This work has resulted in a comprehensive global map of the entire N4-like viral lineage, including information on their distribution in different biomes, evolutionary divergence, genomic diversity, and the potential for viral-mediated host metabolic reprogramming. As such, this work significantly contributes to our understanding of the ecological function and viral-host interactions of bacteriophages.
