title: Use of host-like peptide motifs in viral proteins is a prevalent strategy in host-virus interactions.
abstract: Viruses interact extensively with host proteins, but the mechanisms controlling these interactions are not well understood. We present a comprehensive analysis of eukaryotic linear motifs (ELMs) in 2,208 viral genomes and reveal that viruses exploit molecular mimicry of host-like ELMs to possibly assist in host-virus interactions. Using a statistical genomics approach, we identify a large number of potentially functional ELMs and observe that the occurrence of ELMs is often evolutionarily conserved but not uniform across virus families. Some viral proteins contain multiple types of ELMs, in striking similarity to complex regulatory modules in host proteins, suggesting that ELMs may act combinatorially to assist viral replication. Furthermore, a simple evolutionary model suggests that the inherent structural simplicity of ELMs often enables them to tolerate mutations and evolve quickly. Our findings suggest that ELMs may allow fast rewiring of host-virus interactions, which likely assists rapid viral evolution and adaptation to diverse environments.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, 600 16(th) Street, GH-S572, UCSF Box 2280, San Francisco, CA 94143-2280, USA.
authors.forename: Tzachi
authors.initials: T
authors.lastname: Hagai
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel.
authors.forename: Ariel
authors.initials: A
authors.lastname: Azia
authors.affiliation: The Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: madanm@mrc-lmb.cam.ac.uk.
authors.forename: M Madan
authors.initials: MM
authors.lastname: Babu
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, 600 16(th) Street, GH-S572, UCSF Box 2280, San Francisco, CA 94143-2280, USA. Electronic address: raul.andino@ucsf.edu.
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019143:Evolution, Molecular; D015894:Genome, Human; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014764:Viral Proteins