Use of host-like peptide motifs in viral proteins is a prevalent strategy in host-virus interactions

Tzachi Hagai, Ariel Azia, M. Madan Babu*, Raul Andino

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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.

Original languageEnglish
Pages (from-to)1729-1739
Number of pages11
JournalCell Reports
Issue number5
StatePublished - 12 Jun 2014
Externally publishedYes


FundersFunder number
Human Frontier Science Program Long-Term Fellowship
National Institutes of Health
National Institute of Allergy and Infectious DiseasesP01AI091575, R21AI040085, R01 AI36178
Defense Advanced Research Projects Agency
European Molecular Biology Organization
Medical Research CouncilMC_U105185859
Human Frontier Science ProgramRGY0073/2010


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