title: The pyrimidine analog FNC inhibits cell proliferation and viral protein synthesis in HTLV‑1‑infected cells.
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.
authors.affiliation: Research Center for Immunology, Xinxiang Medical University, Xinxiang, Henan 453003, PR China.
authors.forename: Jinheng
authors.initials: J
authors.lastname: Wang
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Cai
authors.initials: C
authors.lastname: Gao
authors.forename: Xiangfeng
authors.initials: X
authors.lastname: Song
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Niu
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Gao
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
authors.forename: Junbiao
authors.initials: J
authors.lastname: Chang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D001386:Azides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015490:HTLV-I Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects*; D011743:Pyrimidines / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis*
chemical_list: D001386:Azides; D011743:Pyrimidines; D014764:Viral Proteins; D003841:Deoxycytidine; C540945:azvudine