Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Retrovirology. 2011 Dec 16;8:104. doi: 10.1186/1742-4690-8-104.

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

Author information

  • 1Inserm, U1016, Institut Cochin, Paris, France.

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.

© 2011 Cribier et al; licensee BioMed Central Ltd.

PMID:
22176773
[PubMed - indexed for MEDLINE]
PMCID:
PMC3286403
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for BioMed Central Icon for PubMed Central
    Loading ...
    Write to the Help Desk