Rules of engagement: molecular insights from host-virus arms races

Annu Rev Genet. 2012;46:677-700. doi: 10.1146/annurev-genet-110711-155522.


Mammalian genes and genomes have been shaped by ancient and ongoing challenges from viruses. These genetic imprints can be identified via evolutionary analyses to reveal fundamental details about when (how old), where (which protein domains), and how (what are the functional consequences of adaptive changes) host-virus arms races alter the proteins involved. Just as extreme amino acid conservation can serve to identify key immutable residues in enzymes, positively selected residues point to molecular recognition interfaces between host and viral proteins that have adapted and counter-adapted in a long series of classical Red Queen conflicts. Common rules for the strategies employed by both hosts and viruses have emerged from case studies of innate immunity genes in primates. We are now poised to use these rules to transition from a retrospective view of host-virus arms races to specific predictions about which host genes face pathogen antagonism and how those genetic conflicts transform host and virus evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Carrier Proteins / genetics
  • Cytidine Deaminase
  • Cytosine Deaminase / genetics
  • Epistasis, Genetic
  • Evolution, Molecular*
  • Host-Pathogen Interactions*
  • Humans
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism
  • Proteolysis
  • Retroviridae / genetics
  • Retroviridae / immunology
  • Retroviridae / pathogenicity
  • Retroviridae Infections / genetics
  • Retroviridae Infections / immunology
  • Retroviridae Infections / virology
  • SAM Domain and HD Domain-Containing Protein 1
  • Selection, Genetic
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • Carrier Proteins
  • Tripartite Motif Proteins
  • Viral Proteins
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases
  • SAM Domain and HD Domain-Containing Protein 1
  • SAMHD1 protein, human
  • Cytosine Deaminase
  • APOBEC3 protein, human
  • Cytidine Deaminase
  • Monomeric GTP-Binding Proteins