Interleukin-4 up-regulates T-tropic human immunodeficiency virus type 1 transcription in primary CD4+ CD38+ T-lymphocyte subset.
The capacity of human immunodeficiency virus type 1 (HIV-1) to infect resting cells and to produce progeny particles may contribute significantly to its pathogenicity in vivo. We previously reported that primary culture of resting CD4(+) CD38(+) T-lymphocyte subset had higher production rate of CXCR4-using (X4) HIV-1 than CD4(+) CD38(-) subset. Interleukin (IL)-4 highly contributed to the up-regulation of the X4 virus production in the CD38(+) subset. Here, we show evidences that IL-4 treatment of both resting CD38(+) and CD38(-) subsets allowed the adsorption, entry, and integration of X4 virus at similar rates, while the following viral transcription rate was significantly lower in the CD38(-) than CD38(+) subset. Treatment of the CD38 subsets with IL-4 or phytohemagglutinin revealed no association of X4 virus replication ability in the subsets with classic T-cell activation or proliferation. Interestingly, the activator protein (AP)-1 was significantly activated in the CD38(+) subset after IL-4 treatment, while both nuclear factor (NF)-kappaB and signal transducers and activator of transcription (STAT)-6 were activated in the IL-4-treated CD38(-) and CD38(-) subsets at similar levels. Thus, IL-4-dependent X4 HIV-1 transcription occurs efficiently in the CD38(+) but not CD38(-) subset of CD4(+) population and AP-1 could play a significant role on viral transcription, leading to the up-regulated X4 virus production in the CD38(+) subset.
Li
Yong-Gang
YG
Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
Iwabu
Yukie
Y
Warachit
Jiranan
J
Kinomoto
Masanobu
M
Ibrahim
Madiha S
MS
Tsuji
Shoutaro
S
Mukai
Tetsu
T
Kameoka
Masanori
M
Tokunaga
Kenzo
K
Sata
Tetsutaro
T
Ikuta
Kazuyoshi
K
D036541:ADP-ribosyl Cyclase / Q000032:analysis* / Q000276:immunology; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000032:analysis* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D002478:Cells, Cultured; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear; D008562:Membrane Glycoproteins; D018808:Transcription Factor AP-1 / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation; D014779:Virus Replication
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D018808:Transcription Factor AP-1; D015847:Interleukin-4; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1