Interleukin-4 Up-Regulates T-Tropic Human Immunodeficiency Virus Type 1 Transcription in Primary CD4+ CD38+ T-Lymphocyte Subset

• Published in: Microbiology and immunology 2005-01, Vol.49 (2), p.155-165
• Main Authors: Li, Yong-Gang, Iwabu, Yukie, Warachit, Jiranan, Kinomoto, Masanobu, Ibrahim, Madiha S., Tsuji, Shoutaro, Mukai, Tetsu, Kameoka, Masanori, Tokunaga, Kenzo, Sata, Tetsutaro, Ikuta, Kazuyoshi
• Format: Article
• Language: English
• Subjects: ADP-ribosyl Cyclase - analysis; ADP-ribosyl Cyclase - immunology; ADP-ribosyl Cyclase 1; Antigens, CD - analysis; Antigens, CD - immunology; AP-1; CD38; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cells, Cultured; HIV-1; HIV-1 - genetics; Humans; IL-4; Interleukin-4 - pharmacology; Leukocytes, Mononuclear; Membrane Glycoproteins; transcription; Transcription Factor AP-1 - biosynthesis; Transcription, Genetic - drug effects; Up-Regulation; Virus Replication
• ISSN: 0385-5600; 1348-0421
• DOI: 10.1111/j.1348-0421.2005.tb03715.x

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)‐κB 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.