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  HIV-1 IN/Pol recruits LEDGF/p75 into viral particles

Desimmie, B. A., Weydert, C., Schrijvers, R., Vets, S., Demeulemeester, J., Proost, P., et al. (2015). HIV-1 IN/Pol recruits LEDGF/p75 into viral particles. RETROVIROLOGY, 12: 16. doi:10.1186/s12977-014-0134-4.

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 Creators:
Desimmie, Belete Ayele1, Author
Weydert, Caroline1, Author
Schrijvers, Rik1, Author
Vets, Sofie1, Author
Demeulemeester, Jonas1, Author
Proost, Paul1, Author
Paron, Igor2, Author              
De Rijck, Jan1, Author
Mast, Jan1, Author
Bannert, Norbert1, Author
Gijsbers, Rik1, Author
Christ, Frauke1, Author
Debyser, Zeger1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTIONAL COACTIVATOR LEDGF/P75; INTEGRASE INHIBITOR; HUMAN-CELLS; ALLOSTERIC INHIBITORS; GROWTH-FACTOR; PWWP DOMAIN; REPLICATION; PROTEIN; MECHANISMIntegrase; LEDGF/p75; Protease; Protease cleavage sites; Assembly;
 Abstract: Background: The dynamic interaction between HIV and its host governs the replication of the virus and the study of the virus-host interplay is key to understand the viral lifecycle. The host factor lens epithelium-derived growth factor (LEDGF/p75) tethers the HIV preintegration complex to the chromatin through a direct interaction with integrase (IN). Small molecules that bind the LEDGF/p75 binding pocket of the HIV IN dimer (LEDGINs) block HIV replication through a multimodal mechanism impacting early and late stage replication including HIV maturation. Furthermore, LEDGF/p75 has been identified as a Pol interaction partner. This raised the question whether LEDGF/p75 besides acting as a molecular tether in the target cell, also affects late steps of HIV replication. Results: LEDGF/p75 is recruited into HIV-1 particles through direct interaction with the viral IN (or Pol polyprotein) and is a substrate for HIV-1 protease. Incubation in the presence of HIV-1 protease inhibitors resulted in detection of full-length LEDGF/p75 in purified viral particles. We also demonstrate that inhibition of LEDGF/p75-IN interaction by specific mutants or LEDGINs precludes incorporation of LEDGF/p75 in virions, underscoring the specificity of the uptake. LEDGF/p75 depletion did however not result in altered LEDGIN potency. Conclusion: Together, these results provide evidence for an IN/Pol mediated uptake of LEDGF/p75 in viral particles and a specific cleavage by HIV protease. Understanding of the possible role of LEDGF/p75 or its cleavage fragments in the viral particle awaits further experimentation.

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Language(s): eng - English
 Dates: 2015
 Publication Status: Published online
 Pages: 15
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000350793700001
DOI: 10.1186/s12977-014-0134-4
 Degree: -

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Title: RETROVIROLOGY
Source Genre: Journal
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Publ. Info: 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND : BIOMED CENTRAL LTD
Pages: - Volume / Issue: 12 Sequence Number: 16 Start / End Page: - Identifier: ISSN: 1742-4690