Block T M, Lu X, Platt F M, Foster G R, Gerlich W H, Blumberg B S, Dwek R A
Jefferson Cancer Institute, Jefferson Medical College, Philadelphia, PA 19107.
Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2235-9. doi: 10.1073/pnas.91.6.2235.
The imino sugar N-butyldeoxynojirimycin (NBDNJ) is a potent inhibitor of the oligosaccharide-trimming enzyme alpha-glucosidase I. Hepatitis B virus (HBV) contains three surface proteins (HBs proteins) of different sizes that are singly or doubly N-glycosylated and are essential for the formation of infectious virus. Therefore, the replication and secretion of HBV in the human hepatoma cell line HepG2 were studied in the presence of NBDNJ. In the stably HBV-transfected HepG 2.2.15 cells and in HBV-infected HepG2 cells, NBDNJ suppressed secretion of HBV particles and caused intracellular retention of HBV DNA. The secretion of subviral particles was less affected. These data suggest that inhibitors of oligosaccharide trimming may be useful for antiviral therapy of hepatitis B and for the study of the intracellular transport of the viral glycoproteins.
亚氨基糖N-丁基脱氧野尻霉素(NBDNJ)是寡糖修剪酶α-葡萄糖苷酶I的有效抑制剂。乙型肝炎病毒(HBV)含有三种不同大小的表面蛋白(HBs蛋白),这些蛋白单糖基化或双糖基化,对于感染性病毒的形成至关重要。因此,在NBDNJ存在的情况下,研究了HBV在人肝癌细胞系HepG2中的复制和分泌。在稳定转染HBV的HepG 2.2.15细胞和HBV感染的HepG2细胞中,NBDNJ抑制了HBV颗粒的分泌,并导致HBV DNA在细胞内滞留。亚病毒颗粒的分泌受影响较小。这些数据表明,寡糖修剪抑制剂可能对乙型肝炎的抗病毒治疗以及病毒糖蛋白的细胞内运输研究有用。