基因君官网
2016年2月2日讯/生物谷BIOON/德克萨斯大学西南医学中心的研究人员破解了一种由HIV制成的小蛋白质如何引起艾滋病并操纵人类基因最终致命的过程。
“我们已经鉴定了蛋白质分子机制，由艾滋病毒与宿主细胞相互作用形成的Tat蛋白能激活或抑制数百种人类基因，” Iván D’Orso博士说， “调查结果清楚地表明，阻止Tat蛋白活性可能对艾滋病患者的治疗有一定价值。”
我们早就知道，艾滋病病毒会引发艾滋病抑制人体免疫细胞发展，并将它们转换为艾滋病毒制造地，然后杀死其他通常抵抗疾病的免疫细胞。尽管抗逆转录病毒治疗艾滋病的前景已经有所改善，但艾滋病毒也会隐藏在细胞中，并继续破坏宿主的免疫系统。
来自疾病控制和预防中心(CDC) 最新数据表明，在2012年，估计约有120万美国人携带艾滋病毒，其中156，300例病人已经发生感染但没有被诊断出。在美国每年大约有50，000人新发感染艾滋病病毒。2013年，美国疾病控制和预防中心估计，超过26，000美国人会得晚期艾滋病。
像所有的逆转录病毒一样，艾滋病毒很少有自己的基因，它必须借用宿主细胞机制才能传播并蔓延到全身。Iván D’Orso博士说。
“我们发现艾滋病毒精确的操纵着宿主的基因和细胞机制。我们也观察到，艾滋病病毒通过细胞修复防御途径用于其生存。”他补充道。
“我们的研究表明这个小病毒蛋白Tat与大约400个人类基因有直接关联，目的是生成一种适宜艾滋病毒生长的环境。然后，这种蛋白质就完全关闭了人体的免疫防御系统。令人惊讶的是，这么小的病毒蛋白有如此大的能量”D ‘Orso博士说。“Tat操纵的人类基因和通路与这些患者中观察到的症状相关联，如免疫系统过度活化，然后减弱，最后加速老化。”D ‘Orso博士说。
意大利的罗马国立卫生研究所最近完成了一项靶向Tat蛋白的实验性疫苗的II期临床试验。该实验随访了87名艾滋病毒阳性患者长达三年，报道称，该疫苗耐受良好，没有明显的副作用。然而，这也需要数年时间来确定该疫苗是否真的有效，D ‘Orso博士说。
虽然有些人感染艾滋病但没有出现症状，但是当艾滋病毒阻碍身体抵抗疾病的时候艾滋病就已经出现症状了。
（基因宝jiyinbao.com）
本文系生物谷原创编译整理，欢迎转载！点击 获取授权 。更多资讯请下载生物谷APP.
UT Southwestern Medical Center researchers have deciphered how a small protein made by the human immunodeficiency virus (HIV) that causes AIDS manipulates human genes to further its deadly agenda. The findings, published in the online journal eLife, could aid in the search for new or improved treatments for patients with AIDS, or to the development of preventive strategies. “We have identified the molecular mechanisms by which the Tat protein made by HIV interacts with the host cell to activate or repress several hundred human genes,” said Dr. Iván D’Orso, Assistant Professor of Microbiology at UT Southwestern and senior author of the study. “The findings clearly suggest that blocking Tat activity may be of therapeutic value to HIV patients.” It has long been known that HIV causes AIDS by hijacking the body’s immune cells, transforming them into HIV factories and killing other immune cells that normally fight disease. HIV also hides in cells and continues to undermine the host’s immune system despite antiretroviral therapy that has improved the outlook of those with AIDS. The latest data from the Centers for Disease Control and Prevention (CDC), in 2012, estimated 1.2 million Americans were living with HIV, including 156,300 whose infections had not been diagnosed. About 50,000 people in the U.S. are newly infected with HIV annually, the CDC projects. In 2013, the CDC estimated that over 26,000 Americans had the advanced form of HIV infection, AIDS. Like all retroviruses, HIV has very few genes of its own and must take over the host’s cellular machinery in order to propagate and spread throughout the body. Although the broad aspects of that cellular hijacking were known, the nuances remain to be explored, Dr. D’Orso said. “We observed that HIV methodically and precisely manipulates the host’s genes and cellular machinery. We also observed that HIV rewires cellular defensive pathways to benefit survival of the virus,” he added. The study provides insights into HIV’s ability to survive despite antiretroviral therapy, findings that could lead to new therapeutic targets or ways to make current therapies more effective, he said.