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.


RESULTS
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.


CONCLUSIONS
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.
Schüle
Silke
S
Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany.
Kloke
Björn-Philipp
BP
Kaiser
Julia K
JK
Heidmeier
Sabine
S
Panitz
Sylvia
S
Wolfrum
Nina
N
Cichutek
Klaus
K
Schweizer
Matthias
M
D000818:Animals; D015153:Blotting, Western; D016664:Cercocebus; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008957:Models, Genetic; D009000:Monocytes / Q000378:metabolism / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus