Phage adapts to a host modified to hinder the essential recruitment of a host protein No genetic mutations are fixed at the engineered virus-host interaction interface Adaptation is likely linked to phenotypic mutations caused by transcription errors Sub-genomic RNAs may enable this kind of adaptation mechanism in coronaviruses
Viruses repurpose the host molecular machinery for their own proliferation, block host antiviral factors and recruit host proteins for processes essential for virus propagation. Cross-species transmission requires that the virus can establish crucial interactions in the two different environments of the new and the old hosts. To explore the molecular mechanisms behind host promiscuity, we challenged a lytic phage to propagate in a host in which a protein essential for the assembly of a functional viral replisome had been modified to hinder its recruitment. The virus adapted to the engineered host without losing the capability to propagate in the original host, but no mutations that could directly explain the recruitment of the modified protein were fixed in the viral DNA genome. Adaptation, however, correlated with mutations in the gene for the viral RNA polymerase, supporting that transcription errors led to phenotypic mutations that contributed to promiscuous recruitment. Some key molecular interactions need only occur a few times per host cell to allow virus replication. Our results then support that such virus-host interactions may be mediated by mutant proteins present at very low concentrations. The possibility arises that phenotypic mutations facilitate cross-species transmission and contribute to evasion of antiviral strategies.
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