title: Inhibition of retroviral replication by members of the TRIM protein family.
abstract: The TRIM protein family is emerging as a central component of mammalian antiviral innate immunity. Beginning with the identification of TRIM5α as a mammalian post-entry restriction factor against retroviruses, to the repeated observation that many TRIMs ubiquitinate and regulate signaling pathways, the past decade has witnessed an intense research effort to understand how TRIM proteins influence immunity. The list of viral families targeted directly or indirectly by TRIM proteins has grown to include adenoviruses, hepadnaviruses, picornaviruses, flaviviruses, orthomyxoviruses, paramyxoviruses, herpesviruses, rhabdoviruses and arenaviruses. We have come to appreciate how, through intense bouts of positive selection, some TRIM genes have been honed into species-specific restriction factors. Similarly, in the case of TRIMCyp, we are beginning to understand how viruses too have mutated to evade restriction, suggesting that TRIM and viruses have coevolved for millions of years of primate evolution. Recently, TRIM5α returned to the limelight when it was shown to trigger the expression of antiviral genes upon recognition of an incoming virus, a paradigm shift that demonstrated that restriction factors make excellent pathogen sensors. However, it remains unclear how many of ~100 human TRIM genes are antiviral, despite the expression of many of these genes being upregulated by interferon and upon viral infection. TRIM proteins do not conform to one type of antiviral mechanism, reflecting the diversity of viruses they target. Moreover, the cofactors of restriction remain largely enigmatic. The control of retroviral replication remains an important medical subject and provides a useful backdrop for reviewing how TRIM proteins act to repress viral replication.
authors.affiliation: MRC Centre for Medical Molecular Virology, University College, London, UK. adam.fletcher@ucl.ac.uk.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Fletcher
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Towers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D000818:Animals; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D012190:Retroviridae / Q000502:physiology*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; C114030:TRAT1 protein, human