Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1

@article{Sayah2004CyclophilinAR,
  title={Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1},
  author={David M Sayah and Elena Sokolskaja and Lionel Berthoux and Jeremy Luban},
  journal={Nature},
  year={2004},
  volume={430},
  pages={569-573}
}
In Old World primates, TRIM5-α confers a potent block to human immunodeficiency virus type 1 (HIV-1) infection that acts after virus entry into cells. Cyclophilin A (CypA) binding to viral capsid protects HIV-1 from a similar activity in human cells. Among New World primates, only owl monkeys exhibit post-entry restriction of HIV-1 (ref. 1). Paradoxically, the barrier to HIV-1 in owl monkey cells is released by capsid mutants or drugs that disrupt capsid interaction with CypA. Here we show that… 
Cyclophilin A is required for TRIM5α-mediated resistance to HIV-1 in Old World monkey cells
TLDR
RNA interference was used to disrupt CypA in cells from African green monkeys and rhesus macaques to determine whether HIV-1 restriction by Old World monkey TRIM5α is modulated by the CA-CypA interaction, and it was found that CypA inhibits HIV- 1 replication in these cells because it is required for CA recognition by TRIM 5α.
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TLDR
Data suggest that CypA protects HIV-1 from an unknown antiviral activity in human cells, and target cell permissivity increased after loading with heterologous VLPs, consistent with a common saturable target that is epistatic to both TRIM5α and the putative CypA-regulated restriction factor.
Cyclophilin A protects HIV-1 from restriction by human TRIM5α
The capsid (CA) protein lattice of HIV-1 and other retroviruses encases viral genomic RNA and regulates steps that are essential to retroviral invasion of target cells, including reverse
Evolution of Cyclophilin A and TRIMCyp Retrotransposition in New World Primates
TLDR
This study has extensively analyzed representative specimens from all New World primate genera and shown that the retrotransposed CypA copy is only present in Aotus, and has shown that this inserted copy diverged from its original counterpart and that this occurred prior to Aotu radiation, although no positive selection was observed.
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TLDR
It is shown that the Old World monkey, rhesus macaque, also encodes a TRIMCyp protein that has arisen independently from that in owl monkeys, and the lack of activity against HIV-1 suggests that Mamu7 homozygous animals will be null for TRIM5-mediated restriction of HIV- 1 and could contribute to improved animal models for HIV/AIDS.
Cyclophilin A Renders Human Immunodeficiency Virus Type 1 Sensitive to Old World Monkey but Not Human TRIM5α Antiviral Activity
TLDR
It is proposed that cyclophilin A isomerization of a proline residue in the TRIM5α sensitivity determinant of the HIV-1 capsid sensitizes it to restriction by Old World monkey TRim5α.
Target Cell Cyclophilin A Modulates Human Immunodeficiency Virus Type 1 Infectivity
TLDR
It is clearly demonstrated that target cell CypA, and not producer cell CyA, is important for HIV-1 CA-mediated function, and inhibition of HIV- 1 infectivity resulting from virion production in the presence of CsA occurs independently of the CA-CypA interaction.
TRIM5α and Species Tropism of HIV/SIV
TLDR
The TRIM5 genotyping is thought to be important in acquired immunodeficiency syndrome monkey models, and there are significant intraspecies variations in the Rh-TRIM5 gene.
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