ObjectiveAn in-frame stop codon prematurely truncating the transmembrane glycoprotein (TMP) is a common feature of many simian immunodeficiency virus, African green monkey strain (SIVagm) molecular clones. The purpose of this study was to investigate the native form of the SIVagmIMP in a naturally infected African green monkey (AGM) and to study the fate of the stop codon following the passage of SIVagmin primates.DesignPolymerase chain reaction was used to clone the entire intracellular portion of the TMP from: (1) peripheral blood mononuclear cells (PBMC) of the naturally infected AGM 155; (2) an isolate of SIVagm155in rhesus PBMC and (3) PBMC from pig-tailed macaques and AGM experimentally infected with an SIVagmmolecular clone encoding a truncated TMP.ResultsPBMC of the naturally infected AGM contained a ‘swarm‘ of related virus genotypes that encoded a full-length TMP, whereas tissue-culture passage in rhesus PBMC resulted in a prematurely truncated form of the TMP. This premature stop codon persisted in PBMC of monkeys experimentally infected with an SIVagmmolecular clone. Both macaques and AGM of same subspecies as AGM 155 (Cercopithecus pygerythrus) and other subspecies (C. aethiopsandC. sabaeus) became infected with SIVagm155. Genetic drift of this region ofenv, as assessed by calculation of the nucleotide substitution/site/year rate, was similar to that of other retroviruses.ConclusionsThe native form of the SIVagmTMP is a full-length gp40, similar to the SIV macaque (SIVmac) strain and HIV-1. However, passage of SIVagmin tissue culture can result in point mutations that introduce a premature stop codon. This stop codon persists during subsequentin vivopassage of SIVagmin primates. This contrasts with similar studies in macaques infected with SIVmac, in which reversion of the TMP stop codon was observed.