Interleukin-4 Up-Regulates T-Tropic Human Immunodeficiency Virus Type 1 Transcription in Primary CD4 super(+) CD38 super(+) 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 super(+) CD38 super(+) T-lymphocyte subset had higher production rate of CXCR4-using (X4) HIV-1 than CD4 super(+) CD38 super(-) subset. Interleukin (IL)-4 highly contributed to the up-regulation of the X4 virus production in the CD38 super(+) subset. Here, we show evidences that IL-4 treatment of both resting CD38 super(+) and CD38 super(-) 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 super(-) than CD38 super(+) 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 super(+) subset after IL-4 treatment, while both nuclear factor (NF)- Kappa B and signal transducers and activator of transcription (STAT)-6 were activated in the IL-4-treated CD38 super(-) and CD38 super(-) subsets at similar levels. Thus, IL-4-dependent X4 HIV-1 transcription occurs efficiently in the CD38 super(+) but not CD38 super(-) subset of CD4 super(+) population and AP-1 could play a significant role on viral transcription, leading to the up-regulated X4 virus production in the CD38 super(+) subset.