HIV-1初始传播病毒Vpr基因遗传变异对诱导G_2期阻滞及细胞凋亡的影响  

Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G_2 arrest and cell apoptosis

作　　者：赵建元[1,2] 丁寄葳[2] 米泽云 周金明[2] 魏涛[1] 岑山[2] 

机构地区：[1]北京联合大学应用文理学院,北京100192 [2]中国医学科学院医药生物技术研究所,北京100050

出　　处：《遗传》2015年第5期480-486,共7页Hereditas（Beijing)

基　　金：北京联合大学研究生创新基金(编号:12246994501);国家基金委-加拿大国立卫生研究院研究基金课题(CIHR)合作基金(编号:81361128017)资助

摘　　要：人免疫缺陷病毒(HIV-1)急性感染过程中,病毒的遗传多样性显著减少,往往只有一株或几株病毒可以建立有效感染,这种病毒被称为初始传播病毒(Transmitted/Founder virus)。病毒蛋白R(Vpr)是HIV-1的辅助蛋白之一,在病毒复制过程中起重要作用。研究初始传播病毒Vpr基因遗传变异与生物学特征对于阐明病毒建立感染的关键环节具有重要意义。文章利用流式细胞术分析了C亚型HIV-1初始传播病毒株与慢性感染株MJ4的Vpr蛋白诱导细胞G2期阻滞和细胞凋亡的能力。结果显示,初始传播病毒ZM246和ZM247的Vpr诱导细胞G2期阻滞和细胞凋亡的能力显著高于慢性感染株MJ4 Vpr。氨基酸序列分析表明,初始传播病毒Vpr在第77、85和94位上存在高频突变。研究结果提示初始传播病毒可能在病毒感染早期,通过Vpr基因的遗传突变,提升病毒诱导细胞停滞G2期和细胞凋亡的能力,进而促进病毒在宿主体内的复制和传播。In the event of acute infection, only a few HIV-1 viral variants can establish the initial productive clin- ical infection, and these viral variants are known as transmitted/founder viruses （T/F viruses）. As one of the accessory proteins of HIV-1, viral protein R （Vpr） plays an important role in viral replication. Therefore, the characterization of T/F virus Vpr is beneficial to understand how virus replicates in a new host. In this study, flow cytometry was used to analyze the effect of G2 arrest and cell apoptosis induced by the T/F virus Vpr and the chronic strain M J4 Vpr. The results showed that the ability of T/F virus ZM246 Vpr and ZM247 Vpr inducing G2 arrest and cell apoptosis are more potent than the M J4 Vpr. The comparison of protein sequences indicated that the amino acids of 77, 85 and 94 contain high freqency mutations, suggesting that these sites may be involved in inducing G2 arrest and cell apoptosis. Taken together, our work suggests that in acute infections, T/F viruses increase the capacity of G2 arrest and cell apoptosis and promote viral replication and transmission in a new host by Vpr genetic mutation.

关 键 词：人免疫缺陷病毒 初始传播病毒 病毒蛋白R(Vpr) 细胞G2期阻滞 细胞凋亡 

分 类 号：R512.91[医药卫生—内科学]