An active TRIM5 protein in rabbits indicates a common antiviral ancestor for mammalian TRIM5 proteins.
The recent identification of antiretroviral tripartite motif-bearing restriction factors that protect against retroviral infection has revealed a novel branch of innate immunity. The factors target the retroviral capsid and inhibit infectivity soon after the capsid has entered the cytoplasm by an incompletely characterized mechanism. Restriction is species specific. For example, TRIM5alpha from Old World monkeys, but not humans, restricts human immunodeficiency virus type 1 infection. Here, we identify an antiviral TRIM5 molecule in rabbits that is closely related to antiviral TRIM5 of both primates and cattle. We demonstrate that the rabbit TRIM5 protein is active against divergent retroviruses and leads to a strong block to viral DNA synthesis and infectivity. Furthermore, we show that antiviral activity is directed against the viral capsid and that human TRIM5 proteins are dominant negative to restriction in rabbit cells. We propose that the sequence and restriction characteristics conserved between restriction factors from primates, cattle, and rabbits indicate that these factors have evolved from a common ancestor with antiretroviral properties.
Schaller
Torsten
T
MRC Centre for Medical Molecular Virology, Department of Infection, Royal Free and University College Medical School, University College London, 46 Cleveland Street, London, United Kingdom.
Hué
Stéphane
S
Towers
Greg J
GJ
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000502:physiology*; D002417:Cattle; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011323:Primates; D020033:Protein Isoforms; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D020033:Protein Isoforms; D000070584:Tripartite Motif Proteins; D004247:DNA; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases