The Specificity of TRIM5α-Mediated Restriction Is Influenced by Its Coiled-Coil Domain
Volume
84
Pagination
5790 - 5801
Publisher
DOI
10.1128/jvi.02413-09
Journal
Journal of Virology
Issue
ISSN
0022-538X
Metadata
Show full item recordAbstract
ABSTRACT: Retroviruses are both powerful evolutionary forces and dangerous threats to genome integrity. As such, they have imposed strong selective pressure on their hosts, notably triggering the emergence of restriction factors, such as TRIM5α, that act as potent barriers to their cross-species transmission. TRIM5α orthologues from different primates have distinct retroviral restriction patterns, largely dictated by the sequence of their C-terminal PRYSPRY domain, which binds the capsid protein of incoming virions. Here, by combining genetic and functional analyses of human and squirrel monkey TRIM5α, we demonstrate that the coiled-coil domain of this protein, thus far essentially known for mediating oligomerization, also conditions the spectrum of antiretroviral activity. Furthermore, we identify three coiled-coil residues responsible for this effect, one of which has been under positive selection during primate evolution, notably in New World monkeys. These results indicate that the PRYSPRY and coiled-coil domains cooperate to determine the specificity of TRIM5α-mediated capture of retroviral capsids, shedding new light on this complex event.
Authors
Maillard, PV; Ecco, G; Ortiz, M; Trono, DCollections
- Centre for Immunobiology [1121]