TY  - JOUR
A1  - Schüle, Silke
A1  - Kloke, Björn-Philipp
A1  - Kaiser, Julia
A1  - Heidmeier, Sabine
A1  - Panitz, Sylvia
A1  - Wolfrum, Nina
A1  - Cichutek, Klaus
A1  - Schweizer, Matthias
T1  - Restriction of HIV-1 replication in monocytes is abolished by Vpx of SIVsmmPBj
T2  - PLoS One
N2  - 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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/24277
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-242771
SN  - 1932-6203
VL  - 4
IS  - 9: e7098
PB  - PLoS
CY  - Lawrence, Kan.
ER  -