Transportin-SR2 imports HIV into the nucleus

Current Biology : CB
Frauke ChristZeger Debyser

Abstract

The human immunodeficiency virus type 1 (HIV-1) and other lentiviruses have the capacity to infect nondividing cells like macrophages. This requires import of the preintegration complex (PIC) through the nuclear pore. Although many cellular and viral determinants have been proposed, the mechanism leading to nuclear import is not yet understood. Using yeast two-hybrid and pull-down, we identified and validated transportin-SR2 (TRN-SR2) as a bona fide binding partner of HIV-1 integrase. We confirmed the biological relevance of this interaction by RNAi. Depletion of TRN-SR2 interfered with the replication of HIV-1 and HIV-2 but not MoMLV in HeLaP4 cells. Knockdown of TRN-SR2 in primary macrophages likewise interfered with HIV-1 replication. Using Q-PCR, we pinpoint this block in replication to the early steps of the viral lifecycle. A reduction in 2-LTR formation suggests a block in PIC nuclear import upon siRNA-mediated knockdown. Different lines of evidence clearly proved that the late steps of viral replication are not affected. In an in vivo nuclear-import assay using labeled HIV-1 particles, the defect in nuclear import after depletion of TRN-SR2 was directly visualized. In comparison with control cell lines, the great majori...Continue Reading

References

Dec 1, 1991·The Journal of Experimental Medicine·J B WeinbergM H Malim
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·P GallayD Trono
Jun 15, 1999·The Journal of Cell Biology·N KataokaG Dreyfuss
Dec 2, 1999·Methods : a Companion to Methods in Enzymology·J LiuD B DeFranco
Mar 30, 2001·The Journal of Biological Chemistry·C DepienneC Dargemont
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·M C LaiW Y Tarn
Jun 4, 2002·Nature Medicine·Carl D NovinaPhillip A Sharp
Mar 12, 2003·The EMBO Journal·Ming-Chih LaiWoan-Yuh Tarn
Jun 11, 2003·The Journal of Biological Chemistry·Goedele MaertensYves Engelborghs
Jul 11, 2003·The EMBO Journal·Ariberto FassatiJosé-Manuel Mingot
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Peter C ScacheriFrancis S Collins
May 14, 2004·Journal of Virology·Masahiro Yamashita, Michael Emerman
Oct 12, 2004·The Journal of Biological Chemistry·Manuel LlanoEric M Poeschla
Mar 8, 2005·The Journal of Biological Chemistry·Katrien BusschotsZeger Debyser
Apr 28, 2005·The Journal of Biological Chemistry·Stéphane EmilianiRichard Benarous
Nov 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Peter CherepanovAlan Engelman
Nov 29, 2005·Nature Medicine·Angela CiuffiFrederic Bushman
Sep 9, 2006·Science·Manuel LlanoEric M Poeschla
Feb 17, 2007·Nature Reviews. Microbiology·Youichi Suzuki, Robert Craigie
Apr 3, 2007·PLoS Pathogens·Anneleen HombrouckZeger Debyser
Apr 24, 2007·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jan De RijckZeger Debyser
Oct 13, 2007·Nature Reviews. Drug Discovery·Charles Flexner
Jun 11, 2008·Antimicrobial Agents and Chemotherapy·Anneleen HombrouckMyriam Witvrouw

❮ Previous
Next ❯

Citations

Dec 18, 2009·Amino Acids·Awatef Allouch, Anna Cereseto
Jan 12, 2011·Biochemistry·Andrew M L Lever, Kuan-Teh Jeang
Jun 14, 2013·Journal of Medicinal Chemistry·Ya-Qiu LongNouri Neamati
Jan 4, 2013·Journal of Proteome Research·Cameron J SchweitzerMichael Belshan
Sep 29, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jiehua ZhouJohn J Rossi
Mar 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Cristina Di PrimioAnna Cereseto
Feb 7, 2012·The Journal of Biological Chemistry·Zhujun AoXiaojian Yao
Apr 2, 2013·Brain : a Journal of Neurology·Maria J MeliàRamon Martí
Dec 17, 2010·Journal of Virology·Jennifer Cano, Ganjam V Kalpana
Mar 9, 2012·Journal of Virology·Jose Carlos Valle-CasusoFelipe Diaz-Griffero
Nov 6, 2009·Journal of Virology·Lise RivièreAndrea Cimarelli
Oct 7, 2011·Journal of Virology·Eric C LogueNathaniel R Landau
Oct 26, 2012·Journal of Virology·Vaibhav B ShahChristopher Aiken
Mar 20, 2012·Journal of Neuroinflammation·Jonathan BertinMichel J Tremblay
Apr 30, 2013·Retrovirology·Thomas FrickeFelipe Diaz-Griffero
Jul 26, 2013·Retrovirology·João I MamedeValérie Courgnaud
Dec 19, 2008·Retrovirology·Olivier DelelisJean-François Mouscadet
Feb 6, 2009·Retrovirology·Lyubov ZaitsevaAriberto Fassati
Apr 9, 2010·Retrovirology·Anna Bergamaschi, Gianfranco Pancino
Nov 19, 2010·Retrovirology·Nathalie Arhel
Dec 20, 2011·Retrovirology·Alexandra CribierStéphane Emiliani
Feb 1, 2011·Retrovirology·Wannes ThysZeger Debyser
Nov 16, 2011·Retrovirology·Li LiuAine McKnight
Aug 15, 2012·Retrovirology·Steven SantosSergey Iordanskiy
Aug 6, 2010·PLoS Computational Biology·Jamie I MacPhersonDavid L Robertson
May 30, 2009·PLoS Pathogens·Frederic D BushmanSumit K Chanda
Sep 8, 2012·PLoS Pathogens·Amanda J PriceLeo C James

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.