TY - JOUR
T1 - Postentry restriction to human immunodeficiency virus-based vector transduction in human monocytes
AU - Neil, Stuart
AU - Martin, Francisco
AU - Ikeda, Yasuhiro
AU - Collins, Mary
PY - 2001
Y1 - 2001
N2 - Cells of the monocyte lineage can be infected with human immunodeficiency virus type 1 (HIV-1) both during clinical infection and in vitro. The ability of HIV-1-based vectors to transduce human monocytes, monocyte-derived macrophages, and dendritic cells (DCs) was therefore examined, in order to develop an efficient protocol for antigen gene delivery to human antigen-presenting cells. Freshly isolated monocytes were refractory to HIV-1-based vector transduction but became transducible after in vitro differentiation to mature macrophages. This maturation-dependent transduction was independent of the HIV-1 accessory proteins Vif, Vpr, Vpu, and Nef in the packaging cells and of the central polypurine tract in the vector, and it was also observed with a vesicular stomatitis virus-pseudotyped HIV-1 provirus, defective only in envelope and Nef. The level and extent of reverse transcription of the HIV-1-based vector was similar after infection of immature monocytes and of mature macrophages. However, 2LTR vector circles could not be detected in monocytes, suggesting a block to vector nuclear entry in these cells. Transduction of freshly isolated monocytes exposed to HIV-1-based vector could be rescued by subsequent differentiation into DCs. This rescue was induced by fetal calf serum in the DC culture medium, which promoted vector nuclear entry.
AB - Cells of the monocyte lineage can be infected with human immunodeficiency virus type 1 (HIV-1) both during clinical infection and in vitro. The ability of HIV-1-based vectors to transduce human monocytes, monocyte-derived macrophages, and dendritic cells (DCs) was therefore examined, in order to develop an efficient protocol for antigen gene delivery to human antigen-presenting cells. Freshly isolated monocytes were refractory to HIV-1-based vector transduction but became transducible after in vitro differentiation to mature macrophages. This maturation-dependent transduction was independent of the HIV-1 accessory proteins Vif, Vpr, Vpu, and Nef in the packaging cells and of the central polypurine tract in the vector, and it was also observed with a vesicular stomatitis virus-pseudotyped HIV-1 provirus, defective only in envelope and Nef. The level and extent of reverse transcription of the HIV-1-based vector was similar after infection of immature monocytes and of mature macrophages. However, 2LTR vector circles could not be detected in monocytes, suggesting a block to vector nuclear entry in these cells. Transduction of freshly isolated monocytes exposed to HIV-1-based vector could be rescued by subsequent differentiation into DCs. This rescue was induced by fetal calf serum in the DC culture medium, which promoted vector nuclear entry.
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U2 - 10.1128/JVI.75.12.5448-5456.2001
DO - 10.1128/JVI.75.12.5448-5456.2001
M3 - Article
C2 - 11356951
AN - SCOPUS:0035006552
SN - 0022-538X
VL - 75
SP - 5448
EP - 5456
JO - Journal of virology
JF - Journal of virology
IS - 12
ER -