Hypersaline environments close to saturation harbor the highest density of virus-like particles reported for aquatic systems as well as low microbial diversity. Thus, they offer unique settings for studying virus-host interactions in nature. However, no viruses have been isolated so far infecting the two most abundant inhabitants of these systems (that is, the euryarchaeon Haloquadratum walsbyi and the bacteroidetes Salinibacter ruber). Here, using three different co-occurring strains, we have isolated eight viruses infecting the ubiquitous S. ruber that constitute three new different genera (named as 'Holosalinivirus', 'Kryptosalinivirus' and 'Kairosalinivirus') according to their genomic traits, different host range, virus-host interaction capabilities and abundances in natural systems worldwide. Furthermore, to get a more complete and comprehensive view of S. ruber virus assemblages in nature, a microcosm experiment was set with a mixture of S. ruber strains challenged with a brine virus concentrate, and changes of viral populations were monitored by viral metagenomics. Only viruses closely related to kairosalinivirus (strictly lytic and wide host range) were enriched, despite their low initial abundance in the natural sample. Metagenomic analyses of the mesocosms allowed the complete recovery of kairosalinivirus genomes using an ad hoc assembly strategy as common viral metagenomic assembly tools failed despite their abundance, which underlines the limitations of current approaches. The increase of this type of viruses was accompanied by an increase in the diversity of the group, as shown by contig recruitment. These results are consistent with a scenario in which host range, not only virus and host abundances, is a key factor in determining virus fate in nature.