Viral proteins activate PARIS-mediated tRNA degradation and viral tRNAs rescue infection.

Viruses compete with each other for limited cellular resources, and some viruses deliver defense mechanisms that protect the host from competing genetic parasites. PARIS is a defense system, often encoded in viral genomes, that is composed of a 53 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB). Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving the host tRNALys. Phage T5 subverts PARIS immunity through expression of a tRNALys variant that prevents PARIS-mediated cleavage, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids.

Genome sequence and characterization of Streptomyces phages Vanseggelen and Verabelle, representing two new species within the genus Camvirus.

Despite the rising interest in bacteriophages, little is known about their infection cycle and lifestyle in a multicellular host. Even in the model system Streptomyces, only a small number of phages have been sequenced and well characterized so far. Here, we report the complete characterization and genome sequences of Streptomyces phages Vanseggelen and Verabelle isolated using Streptomyces coelicolor as a host. A wide range of Streptomyces strains could be infected by both phages, but neither of the two phages was able to infect members of the closely related sister genus Kitasatospora. The phages Vanseggelen and Verabelle have a double-stranded DNA genome with lengths of 48,720 and 48,126 bp, respectively. Both phage genomes contain 72 putative genes, and the presence of an integrase encoding protein indicates a lysogenic lifestyle. Characterization of the phages revealed their stability over a wide range of temperatures (30-45 °C) and pH values (4-10). In conclusion, Streptomyces phage Vanseggelen and Streptomyces phage Verabelle are newly isolated phages that can be classified as new species in the genus Camvirus, within the subfamily Arquattrovirinae.

Synergy and regulation of antiphage systems: toward the existence of a bacterial immune system?

Bacteria encode a vast repertoire of diverse antiphage defense systems. Recent studies revealed that different defense systems are often encoded within the same genome, raising the question of their possible interactions in a cell. Here, we review the known synergies and coregulations of antiphage systems. The emerging complexities suggest a potential existence of an additional level of organization of antiviral defense in prokaryotes. We argue that this organization could be compared with immune systems of animals and plants. We discuss this concept and explore what it could mean in bacteria.

Systematic and quantitative view of the antiviral arsenal of prokaryotes.

Bacteria and archaea have developed multiple antiviral mechanisms, and genomic evidence indicates that several of these antiviral systems co-occur in the same strain. Here, we introduce DefenseFinder, a tool that automatically detects known antiviral systems in prokaryotic genomes. We use DefenseFinder to analyse 21000 fully sequenced prokaryotic genomes, and find that antiviral strategies vary drastically between phyla, species and strains. Variations in composition of antiviral systems correlate with genome size, viral threat, and lifestyle traits. DefenseFinder will facilitate large-scale genomic analysis of antiviral defense systems and the study of host-virus interactions in prokaryotes.

Belief and adherence to COVID 19-lockdown restrictions in patients with asthma versus other chronic diseases: results from a cross-sectional survey nested in the ComPaRe e-cohort, in France.

BACKGROUND: Asthma patients are under-represented among patients with COVID-19. Their behavior during lockdown and associated restrictions is unknown, as well as whether it was influenced by coexistent cardiovascular conditions. METHODS: We conducted a cross-sectional survey in May 2020, in France, nested in ComPaRe, an e-cohort of adults with chronic diseases. A self-administered questionnaire was mailed to 10,859 people; 3701 fully completed questionnaires. The prevalence of self-reported asthma was 7%. Patients were classified in 4 categories: asthma with (n = 106) or without (n = 149) cardiovascular disease and other diseases with (n = 1186) or without (n = 2260) cardiovascular disease. RESULT: Adherence to movement restrictions during the lockdown was very strong: 89% of participants reported a frequency of outings of "less than once per week" and "once or twice per week" for errands and no family-related outings during the lockdown. This proportion and frequency of outings were similar whatever the chronic disease (p = 0.122). Most patients (96%) reported a high feeling of security during the lockdown, but 95% felt anxious or depressed, with no difference by disease. As compared with patients with controlled asthma, those with uncontrolled asthma more frequently reported complaints related to deteriorated medical follow-up, waived care, anxiety or depression. CONCLUSIONS: Behaviors during the lockdown in France among the asthma population did not differ from patients with other chronic diseases in this cohort, which strengthens hypotheses for specific disease-related susceptibility to explain the low representation of asthmatics among COVID-19 cases. Special attention should be paid to the subgroup of patients with uncontrolled asthma during lockdowns.