Page 24 - O. Microbiology

[O. Microbiology-20]

Effects of novel HEXIM1 Derived Chimeric Proteins on HIV-1

expression and production

Hae-In Kim¹, Ji-Chang You¹˙*

¹Laboratory for Molecular Virology, The Catholic University of Korea, Seoul 06591, Korea

p-TEFb is a multiprotein complex, comprised of CycT1 and CDK9, which plays an essential role in the regulation of
transcription by RNA polymerase II(Pol II). One of the 7SK snRNP components, HEXIM1 inhibits the cyclin-dependent
kinase activity of P-TEFb by concealing CDK9’s substrate-binding site. Viral trans-activator Tat can hijack P-TEFb

from 7SK snRNP and convey it to TAR, which enhances gene expression from the HIV promoter by stably engaging

RNA Pol II. Recently, it has been shown that the chimeric protein HEXIM1-Tat(HT) impedes viral transcription by
contending with Tat for TAR binding.

In this study, we combined HT with an advanced cell-penetrating peptide(ACP) which is developed in our laboratory

and set out to determine whether anti-viral effects are enhanced. The stable expression of ACP-HT or HT-ACP not
only inhibited viral protein expression more effectively than HT but also restrained the infectivity of the progeny

virus. ACP-HT and HT-ACP depleted the p24 level of the supernatant up to 95.7% and 81.3% respectively, while HT
reduced p24 level only up to 52.2%. Taken together, ACP-HT and HT-ACP outperformed the anti-viral effect of HT.

These novel chimeric proteins that inhibit HIV-1 replication efficiently could serve as new candidates for anti-HIV-
1 therapy.