An expanded clade of rodent Trim5 genes

Abstract

Trim5α from primates (including humans), cows, and rabbits has been shown to be an active antiviral host gene that acts against a range of retroviruses. Although this suggests that Trim5α may be a common antiviral restriction factor among mammals, the status of Trim5 genes in rodents has been unclear. Using genomic and phylogenetic analyses, we describe an expanded paralogous cluster of at least eight Trim5-like genes in mice (including the previously described Trim12 and Trim30 genes), and three Trim5-like genes in rats. Our characterization of the rodent Trim5 locus, and comparison to the Trim5 locus in humans, cows, and rabbits, indicates that Trim5 has undergone independent evolutionary expansions within species. Evolutionary analysis shows that rodent Trim5 genes have evolved under positive selection, suggesting evolutionary conflicts consistent with important antiviral function. Sampling six rodent Trim5 genes failed to reveal antiviral activities against a set of eight retroviral challenges, although we predict that such activities exist.

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

“…It has multiple roles in inhibiting retroviral lifecycle, including recognition of the viral capsid by its SPRY/PRY domain [51] and more recently it has been shown to have direct effects on signal transduction pathways that may restrict retroviral replication [52], such as targeting NFκB and inflammasome activity as discussed below. Its close homologue, TRIM22, functions to inhibit HIV budding from infected cells [53].…”

Molecular evolution of the antiretroviral TRIM5 gene

“…TRIM5 homologs have been described in the genomes of primates, mouse, rat, dog, cow, and pig, but are not found in the genome sequence of chicken, suggesting a mammalian origin (Sawyer et al 2007;Tareen et al 2009). Because no TRIM5 ortholog exists in the current release of the single marsupial genome project (opossum), it is possible that TRIM5 may be specific to eutherian mammals.…”

“…3). The genomes of cow, rat, and mouse contain expanded arrays of TRIM5 genes, while the human genome contains a single TRIM5 gene, and the dog genome has lost TRIM5 altogether as the result of a relatively recent gene disruption (Sawyer et al 2007;Tareen et al 2009). In addition to primate orthologs of TRIM5, antiviral activity has been reported for rabbit and cow TRIM5 genes (Schaller et al 2007;Si et al 2006;Ylinen et al 2006).…”

“…So far, no antiviral activity has reported for the TRIM5 genes of mice and rats ( Fig. 3; Tareen et al 2009). It is easy to imagine that TRIM5 gene duplications in certain species (cow, rat, mouse) might have been selectively retained, with new paralogs providing an opportunity for simultaneous selection for multiple CA specificities.…”

“…At least twice in the course of primate evolution TRIM5-cyclophilin A chimeric proteins arose via the capture of new exons (Brennan et al 2008;Liao et al 2007;Newman et al 2008;Nisole et al 2004;Sayah et al 2004;Virgen et al 2008;Wilson et al 2008b). The TRIM family is vigorously engaged in gene duplication Reymond et al 2001;Sardiello et al 2008), and in some mammalian genomes, expansions, inversions, and deletions of the TRIM5 locus itself are evident (Sawyer et al 2007;Tareen et al 2009). Given abundant evidence that retroviral pathogens have been ubiquitously present throughout primate evolution (Gifford and Tristem 2003;Johnson 2008;Lower et al 1996;Mager and Freeman 1995;Sverdlov 2000;Weiss 2006;Blikstad et al 2008), and the variety of retroviruses that are known to colonize extant primates (Vogt 1997), it is reasonable to hypothesize that primate TRIM5α has long played, and continues to play, a role in governing patterns of susceptibility to cross-species transmission and spread (within species) of retroviral pathogens (Song et al 2005a).…”