Page 20 - O. Microbiology

[O. Microbiology-18]

Construction and examination of a new type of Brec1

Recombinase derivatives for the Elimination of HIV Proviral

DNA from the Host Genome

Jun Hyun Bae¹, Ji Chang You¹

¹National Research Laboratory for Molecular Virology, Department of Pathology, School of Medicine, The Catholic

University, Seoul 06591, South Korea

Even though combinatorial antiretroviral therapies (cART), which are used to treat HIV-1 infection, can effectively
suppress and relieve symptoms of AIDS but does not completely eliminate HIV-1 infection. In order to effectively

cure HIV-1 infection, the integrated proviral DNA must be removed from the virus infected host genome. We tried
to develop a therapeutic protein drug using Broad-range recombinase 1 (Brec1) and a novel advanced cell-

penetrating peptide (ACP). The Brec1 has previously been known to efficiently and safely remove integrated provirus
from HIV-1 infected cells. However, it in its current form is difficult to being used as for a protein drug as it cannot

get into cells by itself. To overcome this problem, we fused the Brec1 with ACP, which can be easily internalized into
cells and capable of targeting integrated proviral DNA in HIV-1 infected cells. We observed that the overexpression

of ACP-Brec1 lead to the excision of co-transfected proviral DNA in cell lines. Virus production was also found to
be significantly reduced by HIV-1 p24 ELISA and western blot assay. Therefore, this novel approach using a

combination of Brec1 and ACP might have a great potential to develop a novel fundamental curative HIV-1 therapy.