title: An anti-HIV-1 compound that increases steady-state expression of apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G.
abstract: Human apoplipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) 3G (A3G) is an antiviral protein that blocks HIV-1 replication. However, the antiviral activity of A3G is overcome by the HIV-1 protein Vif. This inhibitory function of Vif is related to its ability to degrade A3G in the proteasome. This finding prompted us to examine the activities of 4-(dimethylamino)-2,6-bis[(N-(2-[(2-nitrophenyl)dithio]ethyl)amino)methyl]pyridine (SN-2) and SN-3. We found that 5 µM SN-2 increases the expression of A3G to a level much higher than that observed in the absence of Vif, without affecting the level of Vif expression. The proteasome inhibitor MG-132 increased the level of both A3G and Vif expression. These results demonstrate that A3G is ubiquitinated and degraded in the proteasome by a factor other than Vif, and that SN-2 selectively inhibits these processes. Furthermore, 5 µM SN-2 significantly inhibited the MAGI cell infectivity of wild-type HIV-1. These findings may contribute to the development of a novel anti-HIV-1 drug.
authors: Department of Bioorganic Medicinal Chemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors: Tomohiko
authors: T
authors: Ejima
authors: Mayuko
authors: M
authors: Hirota
authors: Tamio
authors: T
authors: Mizukami
authors: Masami
authors: M
authors: Otsuka
authors: Mikako
authors: M
authors: Fujita
mesh_terms: D000071480:APOBEC-3G Deaminase; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D015394:Molecular Structure; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D019380:Anti-HIV Agents; D007976:Leupeptins; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde