Host factors mediating HIV-1 replication

Human immunodeficiency virus type 1(HIV-1) infection is the leading cause of death worldwide in adults attributable to infectious diseases. Although the majority of infections are in sub-Saharan Africa and Southeast Asia, HIV-1 is also a major health concern in most countries throughout the globe. While current antiretroviral treatments are generally effective, particularly in combination therapy, limitations exist due to drug resistance occurring among the drug classes. Traditionally, HIV-1 drugs have targeted viral proteins, which are mutable targets. As cellular genes mutate relatively infrequently, host proteins may prove to be more durable targets than viral proteins. HIV-1 replication is dependent upon cellular proteins that perform essential roles during the viral life cycle. Maraviroc is the first FDA-approved antiretroviral drug to target a cellular factor, HIV-1 coreceptor CCR5, and serves to intercept viral–host protein–protein interactions mediating entry. Recent large-scale siRNA and shRNA screens have revealed over 1000 candidate host factors that potentially support HIV-1 replication, and have implicated new pathways in the viral life cycle. These host proteins and cellular pathways may represent important targets for future therapeutic discoveries. This review discusses critical cellular factors that facilitate the successive steps in HIV-1 replication.     

人类免疫缺陷病毒-1型感染对U937前单核细胞基因表达的影响

目的：研究人类免疫缺陷病毒-1型(HIV-1) 急性感染对U937前单核细胞基因表达的影响，探索AIDS的病理机制。方法:应用基因芯片技术分析HIV-1感染2-3 d后U937前单核细胞的550个RNA序列的表达水平,并用半定量RT-PCR加以验证。结果:感染HIV-1 后2-3 d的U937细胞有38 个基因受到不同的调节：26个基因被下调，12个基因上调。这些基因编码着功能各异的宿主 蛋白，这些蛋白质涉及不同的细胞内反应过程，包括受体介导的信号转换、亚细胞信号转导 、 凋亡、转录调节和化学趋向等。结论:HIV-1感染能引起U937前单核细胞 许多基因表达发生改变。