Thread by @simroux_virus

🦠🚨New preprint 🚨🦠 "Cryptic inoviruses are pervasive in bacteria and archaea across Earth’s biomes". biorxiv.org/cgi/content/sh… with @mkrupovic, @reb_daly, @AdairLBorges, @SNayfach, @frederikschu, @joeBondyDenomy, @kcwrighton, @twoyke , @AxelVisel, @kyrpides, et al

Full disclosure: this project kind of branched out into many directions. I'll try to summarize it in a few tweets, but please feel free to ask for more info on specific points and/or read the preprint to get the full picture ! 1/n

First: if you don't know about inoviruses, a great place to start is viralzone.expasy.org/558?outline=al…. These are super cool viruses that you may have heard about for 3 main reasons: their chronic infection, impact on pathogens, and use in biotech. 2/n

Their infection cycle is termed "chronic", i.e. they can infect a host, produce new virions, but contrary to other viruses they don't kill their host cell, instead they nicely release their new virion through membrane pore. (again, great illustration is from viralzone) 3/n

Probably the most famous inovirus was found in vibrio cholerae, and this one was noteworthy because it actually encodes the cholera toxin ! So the phage is what makes you (indirectly) sick (although it still need the bacterial cell) science.sciencemag.org/content/272/52…

Finally, the phage display technology is all based on inoviruses grown on E Coli, and leverage their filamentous virion and simple genome (see a nice explanation here -> )

One thing that's always been weird though: while we were discovering (hundreds of) thousands of new viruses in metagenomes, inoviruses have so far been mostly absent from these dataset. So we are left with the ~ 50 known isolates.

In this work, we show that the inoviruses were actually present in genomes and metagenomes from the beinning, we just weren't good at detecting them (see cacm.acm.org/magazines/2018…). And once we understood how to find them, we collected ~10k of these !

What can we learn from this extended collection ? A lot obviously, and probably some things that are still to be discovered.. but we focused on 3 main points

First - inoviruses are likely not a single family, but likely a full viral order divided into 6 families (figure network ?). Despite their short genome, they also encode also a very large diversity of gene (when considered collectively)

Second - they are associated with virtually all bacteria groups, and surprisingly also some archaea (!!). That's where we teamed up with @reb_daly and @TheWrightonLab to validate this experimentally, using a cultivated strain of these archaea

Third - when residing in a host cell, they can make it resistant to other (completely unrelated) viruses ! This was discovered by @AdairLBorges as part of a beautiful work looking at interactions between inoviruses, other viruse, and the host CRISPR-Cas system

So.. where do that leaves us.. My personal take is that inovirus prevalence, diversity, and impact on microbial communities has been vastly underestimated.

If you are growing / working with a bacterial isolates, chances are it is infected by one (or multiple) inoviruses, which may significantly impact the cell phenotype (see e.g. this nice work in Neisseiria journals.plos.org/plospathogens/…)

And finally, they hold great promises for innovative applications, e.g. heat-resistant protein-based filament, vector for targeted delivery, etc..

So that's it, I feel this thread has been (more than) long enough as it is. But if you want to learn more here's a great review on inovirus biology academic.oup.com/femsre/article… , and here's the link again to our preprint on the "extended inovirus universe" \o/ biorxiv.org/cgi/content/sh…

Extra tweet #1: here's the link to the tool we developed to detect these inoviruses in genomes or metagenomes -> github.com/simroux/Inovir…