CCR5 chemokine receptor gene evolution in New World monkeys (Platyrrhini, Primates): implication on resistance to lentiviruses.
The CC chemokine receptor 5 (CCR5) gene of primates encodes a transmembrane protein involved in cellular signaling of some cell types of the immune system. Numerous studies have shown that this peptide is used by lentiviruses in conjunction with the CD4 receptor to mediate binding and entry in target cells of human and non-human primates. New World monkeys (NWM), differently from their African counterparts, have no description of in natura lentivirus infection. Some evidences suggest that a blockage occurs at the viral entry step of infection. To investigate this possibility, we have cloned and sequenced CCR5 genes from several representatives of Platyrrhini, and compared their sequences with those of other Platyrrhini and Catarrhini species available at public databases. Platyrrhini CCR5 genes were shown to be more genetically diverse than their Catarrhini correlates, and their phylogenetic relationships based on that locus were in agreement with previous studies. Comparison of Platyrrhini and Catarrhini CCR5 consensus sequences evidenced several amino acid residues that differ between both groups, some of which have been experimentally associated with lentiviral interaction. A codon-based positive selection analysis showed that some of these sites seem to be under strong selection for variation among the Platyrrhini but not among Catarrhini species. These results suggest the potential involvement of those sites in the apparent refraction of some NWM to lentiviruses. The high ccr5 genetic diversity observed in Platyrrhini, however, argues for a more extensive infection analysis of diverse NWM species to evaluate this resistance and the potential use of those primates as HIV/AIDS animal models.
Ribeiro
Ieda P
IP
Laboratório de Virologia Molecular, Departamento de Genética, Universidade Federal do Rio de Janeiro, CCS-Bloco A-sala A2-121, Rio de Janeiro, RJ 21949-970, Brazil.
Schrago
Carlos G
CG
Soares
Esmeralda A
EA
Pissinatti
Alcides
A
Seuanez
Hector N
HN
Russo
Claudia A M
CA
Tanuri
Amilcar
A
Soares
Marcelo A
MA
D000222:Adaptation, Physiological / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D002427:Cebidae / Q000235:genetics*; D019143:Evolution, Molecular; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D016180:Lentivirus Infections / Q000235:genetics*; D017958:Lentiviruses, Primate / Q000472:pathogenicity; D008969:Molecular Sequence Data; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D019713:Receptors, CCR5