title: Independent genesis of chimeric TRIM5-cyclophilin proteins in two primate species.
abstract: The host range of retroviruses is influenced by antiviral proteins such as TRIM5, a restriction factor that recognizes and inactivates incoming retroviral capsids. Remarkably, in Owl monkeys (omk), a cyclophilin A (CypA) cDNA has been transposed into the TRIM5 locus, resulting in the expression of a TRIM5-CypA fusion protein (TRIMCyp) that restricts retroviral infection based on the retroviral capsid-binding specificity of CypA. Here, we report that the seemingly improbable genesis of TRIMCyp has, in fact, occurred twice, and pigtailed macaques (pgt) express an independently generated TRIMCyp protein. The omkTRIMCyp and pgtTRIMCyp proteins restrict infection by several lentiviruses, but their specificities are distinguishable. Surprisingly, pgtTRIMCyp cannot bind to or restrict HIV-1 capsids as a consequence of a point mutation close to the Cyp:capsid-binding interface that was acquired during or after transposition of pgtCypA. However, the same mutation confers on pgtTRIMCyp the ability to restrict FIV in the presence of cyclosporin A, a drug that normally abolishes the interaction between pgtTRIMCyp or omkTRIMCyp and lentiviral capsids. Overall, an intuitively unlikely evolutionary event has, in fact, occurred at least twice in primates and represents a striking example of convergent evolution in divergent species.
authors.affiliation: Aaron Diamond AIDS Research Center and Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Virgen
authors.forename: Zerina
authors.initials: Z
authors.lastname: Kratovac
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
authors.forename: Theodora
authors.initials: T
authors.lastname: Hatziioannou
mesh_terms: D000818:Animals; D016645:Aotidae; D002213:Capsid / Q000378:metabolism; D021984:Cyclophilin A / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D019143:Evolution, Molecular; D015497:HIV-1 / Q000276:immunology; D016089:Immunodeficiency Virus, Feline / Q000276:immunology; D008254:Macaca nemestrina; D050506:Mutant Chimeric Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011323:Primates; D011485:Protein Binding; D018626:Retroelements; D012190:Retroviridae / Q000276:immunology*; D013045:Species Specificity
chemical_list: D050506:Mutant Chimeric Proteins; D018626:Retroelements; C526560:TRIM5-cyclophilin A protein, Macaca nemestrina; D021984:Cyclophilin A