Page 22 - O. Microbiology

[O. Microbiology-19]

Identification of A novel protein inhibitor acting on late-

stage of HIV-1 replication

Kyung-Lee Yu¹, Ga-Na Kim¹, Hae-In Kim¹, Yu-Mi Jung¹, Ji-Chang You¹

¹Pathology, The Catholic University, Seoul 06591, Korea

Human immunodeficiency virus type 1 (HIV-1) infection induces innate immune responses mediated mainly by IFN-
I. Recently, an anti-viral IFN-β inducible protein, SCOTIN, have been reported to inhibit the Hepatitis C Virus
replication, so we investigated the effects of SCOTIN on HIV-1 replication.

SCOTIN overexpression reduced the virus replication in both 293T and MT-4 cells. We observed that SCOTIN disrupt
the multimerization of Gag, a structural protein of HIV-1, and virus particle release. It is well known that the HIV-1

hijacks the ESCRT machinery to drive virus release and earlier report shows that SCOTIN has a sequence similarity
with ESCRT component, Tsg101 and ALIX. Therefore, we examined the SCOTIN effect on Tsg101 and ALIX. The

SCOTIN interferes with interaction and co-localization of the Gag with Tsg101 and ALIX at the cell membrane by
altering the intracellular localization of Tsg101 and ALIX.

Our data showed a novel role of SCOTIN in regulating the ESCRT and HIV-1 release. While HIV-1 restriction factors
discovered thus far are mainly block the early stage of HIV-1 lifecycle, SCOTIN inhibits rather the late stage of the

HIV-1 replication, virus assembly/ release. The results thus suggest the possibility of developing a new type of anti-
HIV molecule using SCOTIN.