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Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import.

Abstract : UNLABELLED: ABSTRACT: BACKGROUND: Integration of human immunodeficiency virus type 1 (HIV-1) into a host cell chromosome is an essential step under the control of the viral integrase (IN). Although this enzyme is necessary and sufficient to catalyze the integration reaction in vitro, cellular cofactors are involved in the process in vivo. The chromatin-associated factor LEDGF/p75 interacts with IN and promotes integration to transcription units of the host genome. HIV-1 IN also binds the karyopherin TNPO3, however the significance of this interaction during viral replication remains to be explored. RESULTS: Here we present a functional analysis of IN mutants impaired for LEDGF/p75 and TNPO3 interaction. Among them, IN W131A and IN Q168L, that were previously identified to be deficient for LEDGF/p75 interaction, were also partially impaired for TNPO3 binding. We observed that mutations abolishing IN ability to form tetramers resulted in a severe reduction in LEDGF/p75 binding. In sharp contrast, no correlation could be found between the ability of IN to multimerize and TNPO3 interaction. Most of the mutant viruses were essentially impaired for the integration step whereas the amount of 2-LTR circles, reflecting the nuclear import of the viral DNA, was not significantly affected. CONCLUSION: Our functional analysis of HIV-1 IN mutants reveals distinct structural basis for TNPO3 interaction and suggests that the interaction between IN and TNPO3 is not a major determinant of nuclear import but could take place at a nuclear step prior to integration.
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https://www.hal.inserm.fr/inserm-00674026
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Submitted on : Friday, February 24, 2012 - 5:06:28 PM
Last modification on : Thursday, July 2, 2020 - 5:40:11 PM

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Alexandra Cribier, Emmanuel Ségéral, Olivier Delelis, Vincent Parissi, Aurélie Simon, et al.. Mutations affecting interaction of integrase with TNPO3 do not prevent HIV-1 cDNA nuclear import.. Retrovirology, BioMed Central, 2011, 8 (1), pp.104. ⟨10.1186/1742-4690-8-104⟩. ⟨inserm-00674026⟩

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