How pathogens use linear motifs to perturb host cell networks

•Distantly related pathogens use similar strategies in host cell subversion.•Viruses extensively mimic host short linear motifs to hijack host cell pathways.•Examples of motif mimicry in prokaryotic and eukaryotic parasites are presented.•Host motif mimicry seems to be a common tactic in pathogens from all taxonomic domains.

Molecular mimicry is one of the powerful stratagems that pathogens employ to colonise their hosts and take advantage of host cell functions to guarantee their replication and dissemination. In particular, several viruses have evolved the ability to interact with host cell components through protein short linear motifs (SLiMs) that mimic host SLiMs, thus facilitating their internalisation and the manipulation of a wide range of cellular networks. Here we present convincing evidence from the literature that motif mimicry also represents an effective, widespread hijacking strategy in prokaryotic and eukaryotic parasites. Further insights into host motif mimicry would be of great help in the elucidation of the molecular mechanisms behind host cell invasion and the development of anti-infective therapeutic strategies.