Evolution of nef variants in gut associated lymphoid tissue of rhesus macaques during primary simian immunodeficiency virus infection

• Published in: Virology (New York, N.Y.) N.Y.), 2005-12, Vol.343 (1), p.1-11
• Main Authors: Ndolo, Thomas, Syvanen, Michael, Ellison, Thomas, Dandekar, Satya
• Format: Article
• Language: English
• Subjects: Adaptive; Amino Acid Substitution; Animals; Codon, Nonsense; Conserved Sequence; Disease Models, Animal; Epitopes, T-Lymphocyte - genetics; Evolution; Evolution, Molecular; GALT; Genes, nef; Intestinal Mucosa - virology; Lymphoid Tissue - virology; Macaca mulatta; Mutation; Mutation, Missense; Neutral model; Nuclear Localization Signals - genetics; Phylogeny; Positive selection; Sequence Analysis, DNA; Simian Acquired Immunodeficiency Syndrome - virology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - genetics; SIV-Nef; Synonymous and nonsynonymous
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2005.08.013

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.