Replication protein Rep provides selective advantage to viruses in the presence of CRISPR-Cas immunity

Anti-CRISPR (Acr) phages cooperate to establish a successful infection in CRISPR-containing host. We report here the selective advantage provided by a replicationinitiator, Rep, in the context of CRISPR/Acr interaction. A rep knockout mutantof Sulfolobus islandicus rod-shaped virus 2 produced around 4-fold less virus in a CRISPR-null host, suggesting that, although expendable, Rep is the majorreplication initiator. In addition to Rep-dependent replication initiation from the viralgenomic termini, we detected Rep-independent replication initiation from non-terminal sites. Intriguingly, despite the presence of Acrs, lack of Rep showed aprofound effect on virus propagation in a host carrying CRISPR-Cas immunity.Accordingly, the co-infecting parental virus (rep-containing) outcompeted the knockout mutant much more quickly in the CRISPR-containing host than in CRISPR-null host.