title: The potential significance of adaptive evolution and dimerization in chimpanzee intercellular cell adhesion molecules (ICAMs).
abstract: Cell adhesion molecules are involved in a diverse array of cellular processes. Recent data suggests that human immunodeficiency virus (HIV-1) co-opts their functions, in particular the properties of the intercellular cell adhesion molecules (ICAMs), to enhance viral infection and transmission. To investigate mechanisms that may underlie the non-progression that occurs in immunodeficiency virus-infected chimpanzees, we amplified the protein coding regions of multiple non-human primate ICAMs 1-5 and two ICAM ligands, leukocyte function-associated antigen-1 (LFA-1) and macrophage antigen 1 (Mac-1). We then employed a phylogenetic tree-based approach to comparative genomics, in order to screen for the presence of adaptive changes. Strong Darwinian positive selection in chimpanzee ICAMs 1, 2 and 3 was observed, most markedly in domains that are critical for the integrity and maintenance of ICAM-1 dimerization. As binding of ligands, including the attachment of virions, is influenced by the state of ICAM 1 dimerization, chimpanzee ICAMs may have evolved to modulate their own dimerization. In concert with previous evidence suggesting an ancient retroviral pandemic as a prominent selective force in chimpanzee evolution, adaptation of chimpanzee ICAMs may have effected a mechanism that explains the lack of immunosuppression observed following HIV-1 or simian immunodeficiency virus (SIVcpz) infection.
authors.affiliation: Evolutionary Genomics, Colorado Bioscience Park Center, 12635 East Montview Boulevard, Aurora, Colorado 80010, USA. waltern@ohsu.edu
authors.forename: Nicole A R
authors.initials: NA
authors.lastname: Walter
authors.forename: Justin
authors.initials: J
authors.lastname: Stebbing
authors.forename: Walter
authors.initials: W
authors.lastname: Messier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018420:Ape Diseases / Q000235:genetics* / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000502:physiology; D019281:Dimerization; D018450:Disease Progression; D019143:Evolution, Molecular; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D007113:Immunity, Innate / Q000235:genetics; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D012641:Selection, Genetic; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D015815:Cell Adhesion Molecules