Wainberg M A, Bour S, Geleziunas R, Bentwich Z
Institut Lady-Davis, Hôpital général juif, Côte-Sainte-Catherine Montréal, Québec.
Union Med Can. 1992 Sep-Oct;121(5):307-9, 312-4.
The replication cycle of any virus involves a number of steps, beginning with specific attachment to a cell surface receptor leading eventually to production of progeny viruses by infected cells. In the case of the immunodeficiency virus type-1 (HIV-1), the first step involves a specific interaction between the gp120 viral envelope surface protein and specific CD4 receptor sites at the cell surface. This is followed by penetration of the virus into cells and the formation of proviral double-stranded DNA from single-stranded viral RNA, a process mediated through the action of the viral enzyme called reverse transcriptase. This, in turn, leads to the migration of proviral DNA into the nucleus of the cell and the integration of such DNA within the host cell genome. Finally both viral RNA and viral proteins are produced by the cell's genetic apparatus and new viruses are assembled at the cell surface. The fact that integration of viral DNA into host cell chromosomes occurs means that any cellular replication event will be accompanied by replication of viral DNA. Each of these steps represents a potential target for anti-viral chemotherapy. To date, most efforts to treat HIV-associated disease have focused on the reverse transcription step. In this respect, zidovudine (AZT) has been the most widely used anti-viral drug studied. However, the relative toxicity and lack of efficiency of this drug means that our efforts to develop new therapeutic strategies to combat HIV infection must continue.(ABSTRACT TRUNCATED AT 250 WORDS)
任何病毒的复制周期都包括多个步骤,始于病毒特异性附着于细胞表面受体,最终导致受感染细胞产生子代病毒。就1型免疫缺陷病毒(HIV - 1)而言,第一步涉及病毒包膜表面蛋白gp120与细胞表面特定的CD4受体位点之间的特异性相互作用。接下来是病毒进入细胞,并由单链病毒RNA形成前病毒双链DNA,这一过程由名为逆转录酶的病毒酶介导。这进而导致前病毒DNA迁移到细胞核,并将此类DNA整合到宿主细胞基因组中。最后,细胞的遗传机制产生病毒RNA和病毒蛋白,新病毒在细胞表面组装。病毒DNA整合到宿主细胞染色体中的事实意味着任何细胞复制事件都将伴随着病毒DNA的复制。这些步骤中的每一步都代表了抗病毒化疗的潜在靶点。迄今为止,治疗HIV相关疾病的大多数努力都集中在逆转录步骤上。在这方面,齐多夫定(AZT)是研究最广泛的抗病毒药物。然而,这种药物的相对毒性和低效性意味着我们开发对抗HIV感染新治疗策略的努力必须继续。(摘要截选至250词)