Effect of tenofovir on nucleotidases and cytokines in HIV-1 target cells.
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Biswas N, Rodriguez-Garcia M, Crist SG, Shen Z, Bodwell JE, Fahey JV, Wira CR
Effect of tenofovir on nucleotidases and cytokines in HIV-1 target cells.
PLoS One. 2013 Oct 25;8(10):e78814. doi: 10.1371/journal.pone.0078814. eCollection 2013.
- PubMed ID
- 24205323 [ View in PubMed]
- Abstract
Tenofovir (TFV) has been widely used for pre-exposure prophylaxis of HIV-1 infection with mixed results. While the use of TFV in uninfected individuals for prevention of HIV-1 acquisition is actively being investigated, the possible consequences of TFV exposure for the HIV-target cells and the mucosal microenvironment are unknown. In the current study, we evaluated the effects of TFV treatment on blood-derived CD4(+) T cells, monocyte-derived macrophages and dendritic cells (DC). Purified HIV-target cells were treated with different concentrations of TFV (0.001-1.0 mg/ml) for 2 to 24 hr. RNA was isolated and RT-PCR was performed to compare the levels of mRNA expression of nucleotidases and pro-inflammatory cytokine genes (MIP3alpha, IL-8 and TNFalpha) in the presence or absence of TFV. We found that TFV increases 5'-ecto-nucleotidase (NT5E) and inhibits mitochondrial nucleotidase (NT5M) gene expression and increases 5' nucleotidase activity in macrophages. We also observed that TFV stimulates the expression and secretion of IL-8 by macrophages, DC, and activated CD4(+) T cells and increases the expression and secretion of MIP3alpha by macrophages. In contrast, TFV had no effect on TNFalpha secretion from macrophages, DC and CD4(+) T cells. Our results demonstrate that TFV alters innate immune responses in HIV-target cells with potential implications for increased inflammation at mucosal surfaces. As new preventive trials are designed, these findings should provide a foundation for understanding the effects of TFV on HIV-target cells in microbicide trials.