原创力文档restriction of hiv-1 replication in monocytes is abolished by vpx of sivsmmpbj限制hiv - 1复制在单核细胞由vpx sivsmmpbj的废除.pdfVIP
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restriction of hiv-1 replication in monocytes is abolished by vpx of sivsmmpbj限制hiv - 1复制在单核细胞由vpx sivsmmpbj的废除
Restriction of HIV-1 Replication in Monocytes Is
Abolished by Vpx of SIVsmmPBj
¨ ¨ ¤
Silke Schule, Bjorn-Philipp Kloke, Julia K. Kaiser, Sabine Heidmeier, Sylvia Panitz, Nina Wolfrum , Klaus
Cichutek, Matthias Schweizer*
Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany
Abstract
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 ca
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