Dedera D, Vander Heyden N, Ratner L
Department of Medicine, Washington University, St. Louis, Missouri 63110.
AIDS Res Hum Retroviruses. 1990 Jun;6(6):785-94. doi: 10.1089/aid.1990.6.785.
A series of inhibitors of trimming glucosidases and mannosidases were examined for antiviral activity toward HIV-1. N-butyl deoxynojirimycin (N-buDNJ) was found to be the most potent agent studied. Treatment of acutely infected lymphoid cells with 2.0 mM N-buDNJ reduced virus yield more than 90%, without affecting cell growth. Though lower concentrations of N-buDNJ (0.002-0.2 mM) did not affect HIV-1 production, there was complete inhibition of syncytia formation. Treatment of chronically infected lymphoid cells with 0.1-1.0 mM N-buDNJ resulted in no significant change in virus production, but 80% reduction of infectivity. The attenuation in HIV-1 infectivity was due at least partially to diminished binding to CD4+ lymphoid cells. Chronically infected lymphoid cells treated with 0.02-1.0 mM N-buDNJ for at least 3 days were markedly impaired in their ability to form syncytia with uninfected lymphoid cells. N-buDNJ treatment of HIV-1 infected cells resulted in both a reduction in the cell surface envelope proteins, and an increase in their apparent molecular weight. These results show that N-buDNJ can be used to impair the infectivity of HIV-1 without significant toxicity.
研究了一系列葡糖苷酶和甘露糖苷酶修剪抑制剂对HIV-1的抗病毒活性。发现N-丁基脱氧野尻霉素（N-buDNJ）是所研究的最有效药物。用2.0 mM N-buDNJ处理急性感染的淋巴细胞可使病毒产量降低90%以上，且不影响细胞生长。虽然较低浓度的N-buDNJ（0.002-0.2 mM）不影响HIV-1的产生，但完全抑制了多核巨细胞的形成。用0.1-1.0 mM N-buDNJ处理慢性感染的淋巴细胞，病毒产生量无显著变化，但感染性降低了80%。HIV-1感染性的减弱至少部分归因于与CD4+淋巴细胞结合的减少。用0.02-1.0 mM N-buDNJ处理慢性感染的淋巴细胞至少3天，其与未感染淋巴细胞形成多核巨细胞的能力明显受损。用N-buDNJ处理HIV-1感染的细胞会导致细胞表面包膜蛋白减少，且其表观分子量增加。这些结果表明，N-buDNJ可用于损害HIV-1的感染性而无明显毒性。
