TRIM family proteins: retroviral restriction and antiviral defence

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Abstract
The tripartite motif (TRIM) family is a wide and well conserved family of proteins characterized by a tripartite structure comprising a RING domain, one or two B-boxes and a predicted coiled-coil region. In addition, most TRIM proteins have additional C-terminal domains of various kinds. TRIM19, better known as PML (for promyelocytic leukaemia protein) forms nuclear structures referred to as nuclear bodies. Proteins encoded by various and unrelated viruses have been shown to target PML and to cause the disruption of nuclear bodies, suggesting that these structures might represent an antiviral barrier. TRIM19 has been proposed to be involved in interferon-mediated antiviral response against several viruses, but its direct implication remains controversial. TRIM5α has been recently shown to be responsible for the resistance of primate cells to diverse retrovirus infection. It blocks an early step of retroviral infection prior to reverse transcription. Like its murine cousin, Fv1, TRIM5α restriction is believed to target the capsid protein. How TRIM5α blocks an early step of retroviral replication is still unknown. Diverse hypotheses are being explored. TRIM5α could interfere with the disassembly of viral cores, sequester them in a subcellular compartment, induce their degradation during transit across the cytoplasm or prevent some vital interaction between cellular proteins and viral components. Although very few TRIM proteins have been individually studied, other members of this family have been reported to interfere with viral replication, such as TRIM1 and TRIM22, suggesting viral interference might be a general characteristic of the whole family. The capacity of TRIMs to form high-order molecular-weight structures located in different cellular compartments and their capacity to recruit multiple cellular proteins would allow them to efficiently counteract cellular infection by a wide array of viruses. These observations lead us to discuss the possibility that the TRIM family might represent a new class of antiviral proteins involved in innate immunity.