RESUMO
The human SAMHD1 protein potently restricts lentiviral infection in dendritic cells and monocyte/macrophages but is antagonized by the primate lentiviral protein Vpx, which targets SAMHD1 for degradation. However, only two of eight primate lentivirus lineages encode Vpx, whereas its paralog, Vpr, is conserved across all extant primate lentiviruses. We find that not only multiple Vpx but also some Vpr proteins are able to degrade SAMHD1, and such antagonism led to dramatic positive selection of SAMHD1 in the primate subfamily Cercopithecinae. Residues that have evolved under positive selection precisely determine sensitivity to Vpx/Vpr degradation and alter binding specificity. By overlaying these functional analyses on a phylogenetic framework of Vpr and Vpx evolution, we can decipher the chronology of acquisition of SAMHD1-degrading abilities in lentiviruses. We conclude that vpr neofunctionalized to degrade SAMHD1 even prior to the birth of a separate vpx gene, thereby initiating an evolutionary arms race with SAMHD1.
Assuntos
Cercopithecinae/genética , Evolução Molecular , Interações Hospedeiro-Patógeno , Lentivirus de Primatas/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Sequência de Aminoácidos , Animais , Linhagem Celular , Cercopithecinae/imunologia , Cercopithecinae/virologia , Análise por Conglomerados , Humanos , Lentivirus de Primatas/patogenicidade , Dados de Sequência Molecular , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas Monoméricas de Ligação ao GTP/imunologia , Filogenia , Proteólise , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Proteínas Virais Reguladoras e Acessórias/metabolismoRESUMO
BACKGROUND AND METHODS: A total of 284 non-human primate sera were collected between December 2004 and September 2005 and tested by a commercially available dot immunobinding assay for the antibodies to cercopithecine herpesvirus 1, an alphaherpesvirus with high mortality for infected humans. RESULTS: Seropositive rates were 58% among non-human primates from animal shelters and 38% among those from zoos and academic institutes. Positive reactors were found in three species, the Formosan macaque (Macaca cyclopis; 57%), the cynomolgus macaque (Macaca fascicularis; 11%) and the olive baboon (Papio anubis; 68%). CONCLUSIONS: Our results showed that natural infection by cercopithecine herpesvirus 1 in Formosan macaques was highly prevalent, and to a certain extent reflected the situation of the wild populations in Taiwan. The findings raised the issues of zoonotic public health and the occupational health of primate workers. High positive rate in olive baboons was also found, although, it cannot be ruled out that the positivity was due to cross-reactivity between cercopithecine herpesvirus 1 and other herpesviruses.