Virus-host interactions during chronic infections & diversity and evolution of Pleolipoviruses

Abstract

Viruses are the most abundant biological entities in any given environment. The have the ability to regulate microbial abundances through their lytic cycles, and actively participate in horizontal gene exchange. Intriguingly, not all viruses kill their hosts, as some establish chronic and long-term interactions with their hosts that result in particle production without cell lysis. So far, our knowledge on the impact of chronic viral infections on host metabolism, as well as, on the diversity of viruses performing this life cycle in prokaryotic systems remains scarce. In this work, we isolated and characterized a novel pleomorphic virus from the Pleolipoviridae family - Haloferax pleomorphic virus 1 (HFPV-1) - infecting the archaeon Haloferax volcanii. This virus is able to establish a chronic infection in its host that leads to efficient and constant viral release without significant effects on host fitness nor appearance of resistant cells. Remarkably, infection with HFPV-1 prompted a massive remodeling of host transcriptomic program, while specifically inducing the downregulation of host defense mechanisms. Furthermore, we showed that the outcome of the infection is heavily influenced by the cross talk between HFPV-1 and resident proviruses on the host genome. Additionally, we uncovered that viral infection inhibited the transition into the morphology of host cells in a temperature dependent manner, further highlighting the ecological impacts of chronic infecting viruses. Notably, HFPV-1 exhibits a uniquely broad host range among pleomorphic viruses, as it is capable to infect efficiently a large diversity of hosts including members from different families to the host of isolation, which could prove crucial in the development of novel genetic systems for so far non-manipulable haloarchaea. Furthermore, we greatly expanded the diversity of pleolipoviruses by producing and surveying metagenomic dataset, reveling that the diversity of pleolipoviruses is larger than previously thought. Thus, we propose a new organization for the Pleolipoviridae family, while also providing further evidence that they likely reshaped their genomes through recombination with different groups of plasmids or other mobile genetic elements. Our work demonstrates that pleolipoviruses are far more diverse than previously thought and that they can heavily affect host fitness and ecological role, highlight the importance of understanding these chronic-infecting viruses and their impact on host metabolism and ecology in different environments.