2005
DOI: 10.1073/pnas.0409853102
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Abstract: Primate genomes encode a variety of innate immune strategies to defend themselves against retroviruses. One of these, TRIM5␣, can restrict diverse retroviruses in a species-specific manner. Thus, whereas rhesus TRIM5␣ can strongly restrict HIV-1, human TRIM5␣ only has weak HIV-1 restriction. The biology of TRIM5␣ restriction suggests that it is locked in an antagonistic conflict with the proteins encoding the viral capsid. Such antagonistic interactions frequently result in rapid amino acid replacements at the… Show more

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Cited by 634 publications
(684 citation statements)
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References 36 publications
(30 reference statements)
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“…13 Comparative analysis of the genes that encode APO-BEC3G and TRIM5a has revealed the intensity of the selective pressures resulting from the long-standing conflict between retroviruses and their hosts. 14,15 These two genes/proteins constitute a paradigm of pathogendriven positive selection pressure, not only because of their global elevated K A /K S values, but also by the identification of precise residues and domains under strong positive selection. Analysis of APOBEC3G across primate species reveals many residues in the aminoterminal cytidine deaminase domain that are under positive selection, which coincide indeed with the proposed region of interaction with the human immunodeficiency virus-1 Vif protein.…”
Section: Discussionmentioning
confidence: 99%
“…13 Comparative analysis of the genes that encode APO-BEC3G and TRIM5a has revealed the intensity of the selective pressures resulting from the long-standing conflict between retroviruses and their hosts. 14,15 These two genes/proteins constitute a paradigm of pathogendriven positive selection pressure, not only because of their global elevated K A /K S values, but also by the identification of precise residues and domains under strong positive selection. Analysis of APOBEC3G across primate species reveals many residues in the aminoterminal cytidine deaminase domain that are under positive selection, which coincide indeed with the proposed region of interaction with the human immunodeficiency virus-1 Vif protein.…”
Section: Discussionmentioning
confidence: 99%
“…Arg335 is located in the hypervariable region v1 of the PRYSPRY domain and has been positively selected during recent evolution. 33 Humans, chimpanzees and gorillas are the only known primates to have a positively charged residue at this position. 31 Partly for that reason, the role of this residue in the inability of TRIM5a hu to restrict HIV-1 had been suspected before, 45 but data published so far has suggested that it was only a minor determinant of HIV-1 restriction.…”
Section: Targeted Mutagenesis Of Arg332 and Arg335 Within Pryspry Firmentioning
confidence: 99%
“…32 Particular attention has been given to the v1 region, which is rich in positively (that is, non-randomly) selected aminoacids. 33,34 Versions of human TRIM5a in which short stretches of the v1 region were replaced by those of the macaque orthologue showed restriction activity against HIV-1. 33,35 In particular, substitution of TRIM5a hu arginine 332 for a proline (the aminoacid present at that position in TRIM5a rh ) decreased permissiveness to HIV-1 infection.…”
Section: Introductionmentioning
confidence: 99%
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“…99 Studies with human and rhesus TRIM5a chimeras indicate this SPRY domain determines which retrovirus species are restricted by TRIM5a. [100][101][102] Separate work in owl monkey cells supports this conclusion. 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.…”
Section: Avoiding Host Cell Restrictionsmentioning
confidence: 68%