Positive selection of primate genes that promote HIV-1 replication

Meyerson, Nicholas R.; Rowley, Paul A.; Swan, Christina H.; Le, Dona T.; Wilkerson, Gregory K.; Sawyer, Sara L.

doi:10.1016/j.virol.2014.02.029

Cited by 49 publications

(63 citation statements)

References 69 publications

(114 reference statements)

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“…Their circulating levels of free or unbound cortisol are approximately 100 times greater than that found in humans or Old World primates (Klosterman et al, 1986). They are also frequently used in infectious disease, genetics, pharmacology, behavioral pharmacology, drug addiction, and toxicology research (Tardif et al, 2011b;Myers et al, 2007;Brandler et al, 2012;Meyerson et al, 2014;Rowlett et al, 2005;Valdez et al, 2007;Achat-Mendes et al, 2012). They are also frequently used in infectious disease, genetics, pharmacology, behavioral pharmacology, drug addiction, and toxicology research (Tardif et al, 2011b;Myers et al, 2007;Brandler et al, 2012;Meyerson et al, 2014;Rowlett et al, 2005;Valdez et al, 2007;Achat-Mendes et al, 2012).…”

Section: Research Usesmentioning

confidence: 99%

Nonhuman Primates

Magden

Mansfield²,

Simmons

et al. 2015

Laboratory Animal Medicine

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Section: Research Usesmentioning

confidence: 99%

Nonhuman Primates

Magden

Mansfield²,

Simmons

et al. 2015

Laboratory Animal Medicine

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“…To assess which primate species should be the focus of our screen, we looked at patterns of evolution in the D1 domain across the primate phylogeny. Currently, CD4 sequences exist for 27 different primate species, 14 of which were generated by our group in a previous study (3). We sequenced CD4 from representative individuals of 4 additional species (Nancy Ma's owl monkey, Aotus nancymaae; Azara's owl monkey, Aotus azarae; Spix's owl monkey, Aotus vociferans; and Bolivian/Peruvian squirrel monkey, Saimiri boliviensis) and used the resulting 31-species CD4 data set to model the pattern of substitutions that has occurred along each branch of the primate phylogeny, using PAML (30) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…While the T cell receptor interacts with the presented peptide antigen, the D1 domain of CD4 interacts with an invariant portion of the MHC class II molecule itself (1), an interaction that is expected to be preserved over evolutionary time. Despite this, we and others previously demonstrated that CD4 is evolving under diversifying selection in primates, with natural selection working in favor of new allelic forms (2)(3)(4). This is presumably because the CD4 D1 domain also interacts with the envelope (Env) surface protein of the lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) (Fig.…”

mentioning

confidence: 96%

“…Tit-for-tat evolution such as this is referred to as an evolutionary arms race and results in accelerated evolution at the binding interface of the two interacting proteins (6). Indeed, codons in both primate CD4 and HIV-1 env that correspond to residues in this interaction interface have been previously characterized by us and others to evolve under positive natural selection (2)(3)(4)(7)(8)(9). While these evolutionary findings show that primate CD4 is genetically diverse, the functional significance of this genetic diversity has not been well characterized.…”

mentioning

confidence: 99%

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Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

Meyerson

Sharma

Wilkerson

et al. 2015

J Virol

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Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCENonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals from captive owl monkey populations harbor CD4 alleles that are compatible with a broad collection of HIV-1 isolates, including those isolated from early in infection in highly affected populations and representing diverse subtypes. C D4 is expressed on the surface of a subset of human T cells, where it stimulates interaction between the T cell receptor and major histocompatibility complex class II (MHC-II) molecules expressed on antigen-presenting cells (Fig. 1A). While the T cell receptor interacts with the presented peptide antigen, the D1 domain of CD4 interacts with an invariant portion of the MHC class II molecule itself (1), an interaction that is expected to be preserved over evolutionary time. Despite this, we and others previously demonstrated that CD4 is evolving under diversifying selection in primates, with natural selection working in favor of new allelic forms (2-4). This is presumably because the CD4 D1 domain also interacts with the envelope (Env) surface protein of the lentiviruses human immunodeficiency virus (HIV) and simian immunodefi...

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“…In contrast, proteins comprising the immune systems of multicellular eukaryotes are often involved in evolutionary arms races with pathogens, leading to rapid and highly variable evolutionary trajectories [25–27]. Proteins directly interacting with pathogen factors are expected to evolve particularly rapidly, and genome-wide comparisons have generally supported this expectation [28–30]. No detailed ASR studies have yet been conducted on primary immune receptors, so we have little experimental information about how the evolution of structure-function occurs in these systems, particularly across large evolutionary timescales.…”

Section: Introductionmentioning

confidence: 99%

Resurrecting ancestral structural dynamics of an antiviral immune receptor: adaptive binding pocket reorganization repeatedly shifts RNA preference

et al. 2016

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BackgroundAlthough resurrecting ancestral proteins is a powerful tool for understanding the molecular-functional evolution of gene families, nearly all studies have examined proteins functioning in relatively stable biological processes. The extent to which more dynamic systems obey the same ‘rules’ governing stable processes is unclear. Here we present the first detailed investigation of the functional evolution of the RIG-like receptors (RLRs), a family of innate immune receptors that detect viral RNA in the cytoplasm.ResultsUsing kinetic binding assays and molecular dynamics simulations of ancestral proteins, we demonstrate how a small number of adaptive protein-coding changes repeatedly shifted the RNA preference of RLRs throughout animal evolution by reorganizing the shape and electrostatic distribution across the RNA binding pocket, altering the hydrogen bond network between the RLR and its RNA target. In contrast to observations of proteins involved in metabolism and development, we find that RLR-RNA preference ‘flip flopped’ between two functional states, and shifts in RNA preference were not always coupled to gene duplications or speciation events. We demonstrate at least one reversion of RLR-RNA preference from a derived to an ancestral function through a novel structural mechanism, indicating multiple structural implementations of similar functions.ConclusionsOur results suggest a model in which frequent shifts in selection pressures imposed by an evolutionary arms race preclude the long-term functional optimization observed in stable biological systems. As a result, the evolutionary dynamics of immune receptors may be less constrained by structural epistasis and historical contingency.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0818-6) contains supplementary material, which is available to authorized users.

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Positive selection of primate genes that promote HIV-1 replication

Cited by 49 publications

References 69 publications

Nonhuman Primates

Nonhuman Primates

Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

Resurrecting ancestral structural dynamics of an antiviral immune receptor: adaptive binding pocket reorganization repeatedly shifts RNA preference

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