Abstract
To test the hypothesis that rabbit endogenous lentivirus type K (RELIK) could play a role in shaping the evolution of TRIM5α, the susceptibility of viruses containing the RELIK capsid (CA) to TRIM5 restriction was evaluated. RELIK CA-containing viruses were susceptible to the TRIM5αs from Old World monkeys but were unaffected by most ape or New World monkey factors. TRIM5αs from various lagomorph species were also isolated and tested for anti-retroviral activity. The TRIM5αs from both cottontail rabbit and pika restrict a range of retroviruses, including HIV-1, HIV-2, FIV, EIAV and N-MLV. TRIM5αs from the European and cottontail rabbit, which have previously been found to contain RELIK, also restricted RELIK CA-containing viruses, whereas a weaker restriction was observed with chimeric TRIM5α containing the B30.2 domain from the pika, which lacks RELIK. Taken together, these results could suggest that the pika had not been exposed to exogenous RELIK and that endogenized RELIK might exert a selective pressure on lagomorph TRIM5α.
Highlights
Retroviruses have a unique replication strategy that involves an obligatory integration step where the viral genome is inserted into that of the host
Compared with the non-transduced control, CrFK cells containing the TRIM5a from the European rabbit were about 30-fold ( p 1⁄4 0.0007) less susceptible to EIAVRELIK(CA), whereas the cells containing TRIM5as from the cottontail rabbit and pika showed lower levels of restriction, about ninefold ( p 1⁄4 0.001) or fourfold ( p 1⁄4 0.003) and fourfold ( p 1⁄4 0.003), respectively. These results are consistent with the hypothesis that acquisition of rabbit endogenous lentivirus type K (RELIK) had provided a selective force leading to the evolution of TRIM5a with enhanced restrictive activity directed against RELIK
How can Trim5a from one species recognize and interact with the CA protein of retroviruses from different genera if they share little or no sequence identity? Second, why will Trim5a from multiple species recognize a given virus even though the interacting residues, thought to lie in the variable regions of the Trim5a [30,31], differ significantly? Third, given the wide range of possible interactions reflected by questions one and two, why can a single amino acid change, for example the R332P alteration in human TRIM5a which allows restriction
Summary
Retroviruses have a unique replication strategy that involves an obligatory integration step where the viral genome is inserted into that of the host. TRIM5a orthologues have been isolated from lagomorphs such as the European rabbit and hare [15,34] They restrict a range of retroviruses, including gammaretroviruses and lentiviruses. The two PCR products were used in a second reaction with primer pair TopoRabbitT5F/PIKARev to generate the chimeric TRIM5a that was cloned into pENTR/D-Topo before transferring to pLgatewayIRESEYFP and pLgatewaySN by LR recombination. Sequences of these primers are shown in table 1. CrFK cells were transduced with delivery vectors carrying TRIM5a and the EYFP marker These were challenged with a panel of retroviruses (HIV-1, HIV-2, SIVmac, FIV, EIAV, PFV, SFV, FFV, B-MLV and N-MLV) 2 days post-transduction. The gene sequences determined in this study have been submitted to GenBank (accession nos KC425460 and KC425461)
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Schedule a callMore From: Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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