Rules of Engagement: Molecular Insights from Host-Virus Arms Races

Abstract

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.

cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection

“…IFI16 is noted for rapid evolution in primates and other mammalian lineages (33) and has undergone repeated duplications and diversification, which is especially evident among rodents (34). Although cGAS appears to be a single-copy gene among mammals, it has also undergone rapid evolution in primates, similar to the evolution of several innate defense genes (35). Therefore, consideration of the context of infection, whether specific to cell type or species, will be crucial to further understanding the functional relationships between IFI16 and cGAS.…”

Genetic conflicts: the usual suspects and beyond

“…Hotspots of several neighboring positively selected protein residues are predicted to represent interaction sites that are being continually reshaped by cycles of increased binding and evasion. Implicit in this prediction is the assumption that the same protein domains have been engaged in evasion-binding cycles over millennia (Daugherty and Malik, 2012).…”

“…approach to study the interaction of viruses with the innate immune antiviral systems of mammals and provide a powerful complement to traditional biochemical techniques (Daugherty and Malik, 2012;Meyerson and Sawyer, 2011).…”

A comparative, cross-species investigation of the properties and roles of transferrin- and lactoferrin-binding protein B from pathogenic bacteria

“…Transferrin is proposed to have arisen through a tandem duplication event in ancestral metazoans resulting in the generation of a bi-lobed protein with two homologous lobes capable of binding two iron atoms (Daugherty and Malik 2012;Park et al 1985). It is generally accepted that the progenitor for Lf arose through a Tf gene duplication event that occurred at time period related to the development of the mammalian lineage (Lambert et al 2005), as this ultimately enabled Lf to develop additional roles without compromising the critical role of Tf in iron homeostasis.…”