Selective Inhibitor of Histone Deacetylase 6 (Tubastatin A) Suppresses Proliferation of Hepatitis C Virus Replicon in Culture of Human Hepatocytes

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M. V. Kozlov^1*, A. A. Kleymenova¹, K. A. Konduktorov¹, A. Z. Malikova², and S. N. Kochetkov¹

¹Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991 Moscow, Russia; fax: (495) 135-1405; E-mail: kozlovmv@hotmail.com

²Kazan Federal University, ul. Kremlyovskaya 18, 420008 Kazan, Republic of Tatarstan, Russia; fax: (843) 292-4448; E-mail: rasssl44@gmail.com

^* To whom correspondence should be addressed.

Received March 12, 2014; Revision received April 2, 2014

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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.

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KEY WORDS: human hepatocytes, acetylation of α-tubulin, HDAC6 and SIRT-2, hepatitis C virus replicon

DOI: 10.1134/S0006297914070050

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