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Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems

Liu, Fanwei ; Shimakami, Tetsuro ; Murai, Kazuhisa ; Shirasaki, Takayoshi ; Funaki, Masaya ; Honda, Masao ; Murakami, Seishi ; Yi, Minkyung ; Tang, Hong ; Kaneko, Shuichi

Scientific reports, 2016-08, Vol.6 (1), p.30939-30939, Article 30939 [Periódico revisado por pares]

England: Nature Publishing Group

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Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems
Autor: Liu, Fanwei ; Shimakami, Tetsuro ; Murai, Kazuhisa ; Shirasaki, Takayoshi ; Funaki, Masaya ; Honda, Masao ; Murakami, Seishi ; Yi, Minkyung ; Tang, Hong ; Kaneko, Shuichi
Assuntos: Antagonism ; Antiviral activity ; Antiviral Agents - pharmacology ; Cell culture ; Cell Line, Tumor ; Drug Evaluation, Preclinical ; Drug resistance ; Drug Resistance, Viral - drug effects ; Drug Resistance, Viral - genetics ; Genotypes ; Hepacivirus - physiology ; Hepatitis ; Hepatitis C ; Humans ; Interferon ; MicroRNAs - antagonists & inhibitors ; MicroRNAs - metabolism ; Mutation ; Replication ; Resistant mutant ; Ribonucleic acid ; RNA ; Side effects ; Virus Replication - drug effects
É parte de: Scientific reports, 2016-08, Vol.6 (1), p.30939-30939, Article 30939
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Direct-acting antivirals (DAAs) against Hepatitis C virus (HCV) show effective antiviral activity with few side effects. However, the selection of DAA-resistance mutants is a growing problem that needs to be resolved. In contrast, miR-122 antagonism shows extensive antiviral effects among all HCV genotypes and a high barrier to drug resistance. In the present study, we evaluated three DAAs (simeprevir, daclatasvir, and sofosbuvir) in combination with anti-miR-122 treatment against HCV genotype 1a in cell cultures. We found that combination treatments with anti-miR-122 and a DAA had additive or synergistic antiviral effects. The EC50 values of simeprevir in simeprevir-resistant mutants were significantly decreased by combining simeprevir with anti-miR-122. A similar reduction in EC50 in daclatasvir-resistant mutants was achieved by combining daclatasvir with anti-miR-122. Combination treatment in HCV-replicating cells with DAA and anti-miR-122 sharply reduced HCV RNA amounts. Conversely, DAA single treatment with simeprevir or daclatasvir reduced HCV RNA levels initially, but the levels later rebounded. DAA-resistant mutants were less frequently observed in combination treatments than in DAA single treatments. In summary, the addition of miR-122 antagonism to DAA single treatments had additive or synergistic antiviral effects and helped to efficiently suppress HCV replication and the emergence of DAA-resistant mutants.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Efficient Suppression of Hepatitis C Virus Replication by Combination Treatment with miR-122 Antagonism and Direct-acting Antivirals in Cell Culture Systems

Liu, Fanwei ; Shimakami, Tetsuro ; Murai, Kazuhisa ; Shirasaki, Takayoshi ; Funaki, Masaya ; Honda, Masao ; Murakami, Seishi ; Yi, Minkyung ; Tang, Hong ; Kaneko, Shuichi

England: Nature Publishing Group

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