Restriction of HIV-1 replication in monocytes is abolished by Vpx of SIVsmmPBj

  • Background: Human primary monocytes are refractory to infection with the human immunodeficiency virus 1 (HIV-1) or transduction with HIV-1-derived vectors. In contrast, efficient single round transduction of monocytes is mediated by vectors derived from simian immunodeficiency virus of sooty mangabeys (SIVsmmPBj), depending on the presence of the viral accessory protein Vpx. Methods and Findings: Here we analyzed whether Vpx of SIVsmmPBj is sufficient for transduction of primary monocytes by HIV-1-derived vectors. To enable incorporation of PBj Vpx into HIV-1 vector particles, a HA-Vpr/Vpx fusion protein was generated. Supplementation of HIV-1 vector particles with this fusion protein was not sufficient to facilitate transduction of human monocytes. However, monocyte transduction with HIV-1-derived vectors was significantly enhanced after delivery of Vpx proteins by virus-like particles (VLPs) derived from SIVsmmPBj. Moreover, pre-incubation with Vpx-containing VLPs restored replication capacity of infectious HIV-1 in human monocytes. In monocytes of non-human primates, single-round transduction with HIV-1 vectors was enabled. Conclusion: Vpx enhances transduction of primary human and even non-human monocytes with HIV-1-derived vectors, only if delivered in the background of SIVsmmPBj-derived virus-like particles. Thus, for accurate Vpx function the presence of SIVsmmPBj capsid proteins might be required. Vpx is essential to overcome a block of early infection steps in primary monocytes.

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Metadaten
Author:Silke Schüle, Björn-Philipp Kloke, Julia KaiserGND, Sabine Heidmeier, Sylvia Panitz, Nina Wolfrum, Klaus CichutekGND, Matthias Schweizer
URN:urn:nbn:de:hebis:30:3-242771
DOI:https://doi.org/doi:10.1371/journal.pone.0007098
ISSN:1932-6203
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/19768115
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2009/09/21
Date of first Publication:2009/09/21
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/04/26
Volume:4
Issue:9: e7098
Page Number:10
HeBIS-PPN:303614196
Institutes:Biowissenschaften / Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0