A Trim5-cyclophilin A fusion protein found in owl monkey kidney cells can restrict HIV-1

Abstract

Lv1 restriction of HIV-1 in the cells of Old World monkeys is associated with the expression of the Trim5 gene. Uniquely, in owl monkey kidney cells, HIV-1 restriction is dependent on the ability of incoming viral capsid protein to bind cyclophilin A (CypA). Cloning of the owl monkey Trim5 gene now reveals the presence of an inserted CypA pseudogene within intron 7 of the Trim5 gene. This insertion results in the formation of a chimeric Trim5-CypA transcript. Transfer of a cDNA corresponding to this transcript into human cells confers cyclosporin A-sensitive resistance to HIV-1 infection. The restriction factor appears to be a chimeric protein created by retrotransposon-mediated exon shuffling

Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5α restriction factor

“…The study of HIV-1 capsid mutants suggests that capsid uncoating may be a temporally regulated process, with either too rapid or too slow disassembly compromising virus infectivity (29). Host cell factors involved in uncoating are unknown (21,30,31). Given this sparse state of knowledge, TRIM5␣-mediated restriction could conceivably involve prevention of capsid uncoating, acceleration of capsid uncoating, or destruction of the capsid.…”

“…Second, when introduced into cells, assembled and proteolytically processed capsids of virus-like particles, but not monomeric capsid proteins expressed in the cells, can compete for the restriction factor(s) (14,16,18,19). Third, TRIMCyp is an HIV-1-restricting factor in owl monkeys consisting of the RBCC domains of TRIM5 fused with cyclophilin A, a known capsid ligand (14,(18)(19)(20)(21)(22)(23). Finally, an association of TRIM5␣ hu with capsids prepared by detergent treatment of a restricted murine leukemia virus (MLV) has been observed (24).…”

Extensive Structural Renovation of Retrogenes in the Evolution of the Populus Genome

“…However, by chance, if the retrocopy fortunately recruits new regulatory elements, it might become a functional retrogene. Moreover, if the retrogene recruits some new coding regions that do not exist in the parental gene, it becomes a retroposed chimeric gene (Betrán et al, 2002;Wang et al, 2002;Nisole et al, 2004;Sayah et al, 2004;Zhang et al, 2004).…”

Intracellular trafficking of retroviral vectors: obstacles and advances

“…These cells contain an unusual TRIM5-Cyclophilin A (TRIMCypA)-fusion protein, arising from retrotransposition of a CypA pseudogene into the TRIM5a locus, replacing the TRIM5a SPRY domain for CypA. 103,104 TRIM-CypA restricts HIV-1 infection in owl monkey cells. 103,104 The CypA portion of TRIM-CypA also binds HIV-1 CA in vitro, 104 like human CypA binds HIV-1 CA.…”

“…103,104 TRIM-CypA restricts HIV-1 infection in owl monkey cells. 103,104 The CypA portion of TRIM-CypA also binds HIV-1 CA in vitro, 104 like human CypA binds HIV-1 CA. 105 This suggests the CypA portion of TRIM-CypA binds HIV-1 CA in vivo in place of the lost SPRY domain while the N-terminal TRIM motifs restrict virus infection.…”