Analysis of the Viral Elements Required in the Nuclear Import of HIV-1 DNA
- 15 January 2010
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 84 (2), 729-739
- https://doi.org/10.1128/jvi.01952-09
Abstract
HIV-1 possesses an exquisite ability to infect cells independently from their cycling status by undergoing an active phase of nuclear import through the nuclear pore. This property has been ascribed to the presence of karyophilic elements present in viral nucleoprotein complexes, such as the matrix protein (MA); Vpr; the integrase (IN); and a cis -acting structure present in the newly synthesized DNA, the DNA flap. However, their role in nuclear import remains controversial at best. In the present study, we carried out a comprehensive analysis of the role of these elements in nuclear import in a comparison between several primary cell types, including stimulated lymphocytes, macrophages, and dendritic cells. We show that despite the fact that none of these elements is absolutely required for nuclear import, disruption of the central polypurine tract-central termination sequence (cPPT-CTS) clearly affects the kinetics of viral DNA entry into the nucleus. This effect is independent of the cell cycle status of the target cells and is observed in cycling as well as in nondividing primary cells, suggesting that nuclear import of viral DNA may occur similarly under both conditions. Nonetheless, this study indicates that other components are utilized along with the cPPT-CTS for an efficient entry of viral DNA into the nucleus.Keywords
This publication has 110 references indexed in Scilit:
- Cyclophilin A-Dependent Restriction of Human Immunodeficiency Virus Type 1 Capsid Mutants for Infection of Nondividing CellsJournal of Virology, 2008
- Global Analysis of Host-Pathogen Interactions that Regulate Early-Stage HIV-1 ReplicationCell, 2008
- Characterization of the Early Steps of Infection of Primary Blood Monocytes by Human Immunodeficiency Virus Type 1Journal of Virology, 2008
- Identification of Host Proteins Required for HIV Infection Through a Functional Genomic ScreenScience, 2008
- HIV-1 DNA Flap formation promotes uncoating of the pre-integration complex at the nuclear poreThe EMBO Journal, 2007
- Human Immunodeficiency Virus Bearing a Disrupted Central DNA Flap Is Pathogenic In VivoJournal of Virology, 2007
- Novel Nuclear Import of Vpr Promoted by Importin α Is Crucial for Human Immunodeficiency Virus Type 1 Replication in MacrophagesJournal of Virology, 2007
- Nuclear Import Defect of Human Immunodeficiency Virus Type 1 DNA Flap Mutants Is Not Dependent on the Viral Strain or Target Cell TypeJournal of Virology, 2006
- HIV-1 integrase is capable of targeting DNA to the nucleus via an Importin α/β-dependent mechanismBiochemical Journal, 2006
- Evidence for a Functional Link between Uncoating of the Human Immunodeficiency Virus Type 1 Core and Nuclear Import of the Viral Preintegration ComplexJournal of Virology, 2006