title: Selective inhibitor of histone deacetylase 6 (tubastatin A) suppresses proliferation of hepatitis C virus replicon in culture of human hepatocytes.
abstract: Acetylation of α-tubulin was studied in cultures of human hepatocytes under the influence of selective inhibitors of histone deacetylases HDAC6 and SIRT-2 - tubastatin A and 2-(3-phenethoxyphenylamino)benzamide, respectively. It was found that in hepatocyte cell line HepG2 acetylated α-tubulin is accumulated preferentially on inhibition of HDAC6 but not of SIRT-2. Under the same conditions, no acetylation of α-tubulin was observed in hepatocyte cell line Huh7. However, the inhibition of HDAC6 with tubastatin A led to hyperacetylation of α-tubulin and simultaneously to decrease in viral RNA concentration in hepatocyte cell line Huh7-luc/neo, which supports propagation of the full genome replicon of hepatitis C virus. The correlation between these two processes points to HDAC6 as a promising cellular target for therapy of hepatitis C.
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia. kozlovmv@hotmail.com.
authors.forename: M V
authors.initials: MV
authors.lastname: Kozlov
authors.forename: A A
authors.initials: AA
authors.lastname: Kleymenova
authors.forename: K A
authors.initials: KA
authors.lastname: Konduktorov
authors.forename: A Z
authors.initials: AZ
authors.lastname: Malikova
authors.forename: S N
authors.initials: SN
authors.lastname: Kochetkov
mesh_terms: D000107:Acetylation; D000998:Antiviral Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D056945:Hep G2 Cells; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D012093:Replicon / Q000235:genetics; D056565:Sirtuin 2 / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; D014404:Tubulin; C553587:tubastatin A; C474199:SIRT2 protein, human; D056565:Sirtuin 2; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases