Identification of nucleotides in the 5′UTR and amino acids substitutions that are essential for the infectivity of 5′UTR-NS5A recombinant of hepatitis C virus genotype 1b (strain Con1)
Identification of nucleotides in the 5′UTR and amino acids substitutions that are essential for the infectivity of 5′UTR-NS5A recombinant of hepatitis C virus genotype 1b (strain Con1)
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DOI：
10.1016/j.virol.2018.03.001
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发表时间：
2018-05-01
期刊：
影响因子：
3.7
通讯作者：
Li, Yi-Ping
中科院分区：
文献类型：
--
作者：
Li, Jinqian;Feng, Shengjun;Li, Yi-Ping
Genotype 1b strain Con1 represents an important reference in the study of hepatitis C virus (HCV). Here, we aimed to develop an advanced infectious Con1 recombinant. We found that previously identified mutations A1226G/F1464L/A1672S/Q1773H permitted culture adaption of Con1 Core-NS5A (C-5A) recombinant containing 5'UTR and NS5B-3'UTR from JFH1 (genotype 2a), thus acquired additional mutations L725H/F886L/D2415G. C-5A containing all seven mutations (C-5A_7m) replicated efficiently in Huh7.5 and Huh7.5.1 cells and had an increased infectivity in SEC14L2-expressing Huh7.5.1 cells. Incorporation of Con1 NS5B was deleterious to C-5A_7m, however Con1 5'UTR was permissive but attenuated the virus. Nucleotides G1, A4, and G35 primarily accounted for the viral attenuation without affecting RNA translation. C-5A_7m was inhibited dose dependently by simeprevir and daclatasvir, and substitutions at A4, A29, A34, and G35 conferred resistance to miR-122 antagonism. The novel Con1 5'UTR-NS5A recombinant, adaptive mutations, and critical nucleotides described here will facilitate future studies of HCV culture systems and virus-host interaction.
