HDAC6 Inhibits HSV-1 Intracellular Transport

Herpes simplex virus type I(HSV-1) is a double-stranded DNA virus, which is common to humans. Epithelial cells is susceptible to HSV-1 infection, which causes herpes labialis, et al. Besides, HSV-1 can transmit from the primary lesion to the nerve tissue and establish a latent infection in trigeminal ganglia. Reactivation of HSV-1 can easily cause neurological disorders.Our previous studies found that in the early infection process, HSV-1 stimulated the expression of acetylated α-tubulin, which thereby stabilized the microtubules for HSV-1 intracellular nuclear transport. Histone deacetylase 6(HDAC6) is an important enzyme controlling the deacetylation of α-tubulin. HDAC6 is the only one of HDACs family to distribute in the cytoplasm, which regulates a variety of post-translational modifications of cytoplasmic proteins. In this study, we investigate the role of HDAC6 in HSV-1 infection process.First, we found that expression of HDAC6 was down-regulated and acetylated α-tubulin was up-regulated during early phase of HSV-1 infection(2/4/6h). Up-regulation of acetylated HSP90 was also detected using IP/WB. Using TSA to inhibit HDAC6 or interfering HDAC6 by si RNA promoted the infection of HSV-1. Whereas overexpression of HDAC6 significantly inhibited HSV-1 nuclear transport. In summary, HDAC6 can inhibit HSV-1 infection through regulating the deacetylation of α-tubulin and viral intracellular transport.In addition, we also discussed the potential mechanism of changes in HDAC6. It was found that, HSV-1 infection downregulated Rho A, ROCK1 and ROCK2. However, the proteins, TPPP1 and p300, were increased. Those three factors can lead inhibition of HDAC6 activity. By si RNA interference or overexpression VP22, we found that HSV-1 protein VP22 involved in viral transport into the nuclear regulatory process by influencing TPPP1 and p300.Virus infection is tightly associated with host cell proteins. Therefore, investigating the relationship between virus and host will not only help to control the pathogenesis, but also provide a theoretic basis for finding new antiviral therapeutic targets.