title: Evolution of nef variants in gut associated lymphoid tissue of rhesus macaques during primary simian immunodeficiency virus infection.
abstract: We utilized the simian immunodeficiency virus model of AIDS to examine evolution of nef gene in gut-associated lymphoid tissue (GALT) during primary and early asymptomatic stages of infection. Macaques were infected with a cloned virus, SIVmac239/nef-stop harboring a premature stop codon in the nef gene. Restoration of the nef open reading frame occurred in GALT early at 3 days post-infection. Analysis of nef sequences by phylogenetic tools showed that evolution of nef was neutral thereafter, as evidenced by the ratio of synonymous to nonsynonymous substitutions, a star pattern in unrooted trees and distribution of amino acid replacements fitting a simple Poisson process. Two regions encoding for a nuclear localization signal and a CTL epitope were conserved. Thus, GALT was a site for strong positive selection of functional nef during initial stages of infection. However, evolution of the nef gene thereafter was neutral during early asymptomatic stage of infection.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ndolo
authors.forename: Michael
authors.initials: M
authors.lastname: Syvanen
authors.forename: Thomas
authors.initials: T
authors.lastname: Ellison
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D018389:Codon, Nonsense; D017124:Conserved Sequence; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D019143:Evolution, Molecular; D015754:Genes, nef; D007413:Intestinal Mucosa / Q000821:virology*; D008221:Lymphoid Tissue / Q000821:virology*; D008253:Macaca mulatta; D009154:Mutation; D020125:Mutation, Missense; D019913:Nuclear Localization Signals / Q000235:genetics; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D018984:Epitopes, T-Lymphocyte; D019913:Nuclear Localization Signals