Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.

<h4>Background</h4>Because uncoating of the capsid is linked to reverse transcription, modifications that delay this process lead to the persistence in the cytoplasm of capsids susceptible to recognition by the human restriction factor TRIM5α (hTRIM5α). It is unknown, however, if increas...

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Autores principales:	Emilie Battivelli, Denise Lecossier, François Clavel, Allan J Hance
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b79869c1892d4cfa959d7b50b776bca8
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spelling	oai:doaj.org-article:b79869c1892d4cfa959d7b50b776bca82021-11-18T08:02:20ZDelaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.1932-620310.1371/journal.pone.0052434https://doaj.org/article/b79869c1892d4cfa959d7b50b776bca82013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23320071/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Because uncoating of the capsid is linked to reverse transcription, modifications that delay this process lead to the persistence in the cytoplasm of capsids susceptible to recognition by the human restriction factor TRIM5α (hTRIM5α). It is unknown, however, if increasing the time available for capsid-hTRIM5α interactions would actually render viruses more sensitive to hTRIM5α.<h4>Results</h4>Viral sensitivity to hTRIM5α was evaluated by comparing their replication in human U373-X4 cells in which hTRIM5α activity had or had not been inhibited by overexpression of human TRIM5γ. No differences were observed comparing wild-type HIV-1 and variants carrying mutations in reverse transcriptase or the central polypurine tract that delayed the completion of reverse transcription. In addition, the effect of delaying the onset of reverse transcription for several hours by treating target cells with nevirapine was evaluated using viral isolates with different sensitivities to hTRIM5α. Delaying reverse transcription led to a time-dependent loss in viral infectivity that was increased by inhibiting capsid-cyclophilin A interactions, but did not result in increased viral sensitivity to hTRIM5α, regardless of their intrinsic sensitivity to this restriction factor.<h4>Conclusions</h4>Consistent with prior studies, the HIV-1 capsid can be targeted for destruction by hTRIM5α, but different strains display considerable variability in their sensitivity to this restriction factor. Capsids can also be lost more slowly through a TRIM5α-independent process that is accelerated when capsid-cyclophilin A interactions are inhibited, an effect that may reflect changes in the intrinsic stability of the capsid. Blocking the onset or delaying reverse transcription does not, however, increase viral sensitivity to hTRIM5α, indicating that the recognition of the capsids by hTRIM5α is completed rapidly following entry into the cytoplasm, as previously observed for the simian restriction factors TRIM-Cyp and rhesus TRIM5α.Emilie BattivelliDenise LecossierFrançois ClavelAllan J HancePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e52434 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emilie Battivelli Denise Lecossier François Clavel Allan J Hance Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.
description	<h4>Background</h4>Because uncoating of the capsid is linked to reverse transcription, modifications that delay this process lead to the persistence in the cytoplasm of capsids susceptible to recognition by the human restriction factor TRIM5α (hTRIM5α). It is unknown, however, if increasing the time available for capsid-hTRIM5α interactions would actually render viruses more sensitive to hTRIM5α.<h4>Results</h4>Viral sensitivity to hTRIM5α was evaluated by comparing their replication in human U373-X4 cells in which hTRIM5α activity had or had not been inhibited by overexpression of human TRIM5γ. No differences were observed comparing wild-type HIV-1 and variants carrying mutations in reverse transcriptase or the central polypurine tract that delayed the completion of reverse transcription. In addition, the effect of delaying the onset of reverse transcription for several hours by treating target cells with nevirapine was evaluated using viral isolates with different sensitivities to hTRIM5α. Delaying reverse transcription led to a time-dependent loss in viral infectivity that was increased by inhibiting capsid-cyclophilin A interactions, but did not result in increased viral sensitivity to hTRIM5α, regardless of their intrinsic sensitivity to this restriction factor.<h4>Conclusions</h4>Consistent with prior studies, the HIV-1 capsid can be targeted for destruction by hTRIM5α, but different strains display considerable variability in their sensitivity to this restriction factor. Capsids can also be lost more slowly through a TRIM5α-independent process that is accelerated when capsid-cyclophilin A interactions are inhibited, an effect that may reflect changes in the intrinsic stability of the capsid. Blocking the onset or delaying reverse transcription does not, however, increase viral sensitivity to hTRIM5α, indicating that the recognition of the capsids by hTRIM5α is completed rapidly following entry into the cytoplasm, as previously observed for the simian restriction factors TRIM-Cyp and rhesus TRIM5α.
format	article
author	Emilie Battivelli Denise Lecossier François Clavel Allan J Hance
author_facet	Emilie Battivelli Denise Lecossier François Clavel Allan J Hance
author_sort	Emilie Battivelli
title	Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.
title_short	Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.
title_full	Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.
title_fullStr	Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.
title_full_unstemmed	Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.
title_sort	delaying reverse transcription does not increase sensitivity of hiv-1 to human trim5α.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/b79869c1892d4cfa959d7b50b776bca8
work_keys_str_mv	AT emiliebattivelli delayingreversetranscriptiondoesnotincreasesensitivityofhiv1tohumantrim5a AT deniselecossier delayingreversetranscriptiondoesnotincreasesensitivityofhiv1tohumantrim5a AT francoisclavel delayingreversetranscriptiondoesnotincreasesensitivityofhiv1tohumantrim5a AT allanjhance delayingreversetranscriptiondoesnotincreasesensitivityofhiv1tohumantrim5a
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Delaying reverse transcription does not increase sensitivity of HIV-1 to human TRIM5α.

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