The pyrimidine analog FNC inhibits cell proliferation and viral protein synthesis in HTLV‑1‑infected cells

Wang,Jinheng; Wang,Xia; Gao,Cai; Song,Xiangfeng; Niu,Zhiguo; Gao,Zhitao; Qin,Zhihai; Chang,Junbiao; Wang,Hui

doi:10.3892/mmr.2013.1358

The pyrimidine analog FNC inhibits cell proliferation and viral protein synthesis in HTLV‑1‑infected cells

Authors:
- Jinheng Wang
- Xia Wang
- Cai Gao
- Xiangfeng Song
- Zhiguo Niu
- Zhitao Gao
- Zhihai Qin
- Junbiao Chang
- Hui Wang
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Affiliations: Research Center for Immunology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, P.R. China, Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China
Published online on: March 5, 2013 https://doi.org/10.3892/mmr.2013.1358
Pages: 1656-1660

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Abstract

Human T‑cell leukemia virus type 1 (HTLV‑1), the first retrovirus to be identified, is the etiological agent of an aggressive clonal malignancy of mature CD4+ T lymphocytes known as adult T‑cell leukemia (ATL). The prognosis of ATL patients remains poor despite the availability of a number of clinical chemotherapy drugs. In addition, HTLV‑1‑infected and ATL cells possess an intrinsic resistance to anticancer drugs. 2'‑Deoxy‑2'‑β‑fluoro‑4'‑azidocytidine (FNC) is a novel pyrimidine analog that is efficiently phosphorylated by cellular kinases and is a substrate for RNA and DNA polymerases. In the present study, the antiviral potential of FNC was investigated in HTLV‑1‑infected cell lines. Following FNC treatment, the HTLV‑1‑infected cells underwent G1 or S phase cell cycle arrest. FNC was also observed to reduce cell growth of the HTLV‑1‑infected cell lines in a dose‑dependent manner. Notably, FNC was found to efficiently inhibit the expression of the viral proteins, Tax and p19Gag, in a dose‑ and time‑dependent manner. Treatment with FNC and the protein biosynthesis inhibitor, cycloheximide (CHX), accelerated the inhibition of viral protein synthesis in the HTLV‑1‑infected cells. Collectively, these results demonstrated the efficient antiretroviral effect of FNC in HTLV‑1‑infected cells and indicate that FNC may be utilized as a valuable therapy in HTLV‑1‑infected patients and those with ATL.

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