一项针对接触猴免疫缺损病毒(SIV)---人HIV的动物等同物---的猴子的新研究揭示出在感染的最早期阶段发生了什么。在这个最早期阶段,人们不能够在血液中检测到病毒,而且这个最早期阶段是人体中一段关键性的但是很难研究的时期。这些发现对疫苗开发和制定阻止感染的其他策略具有重要意义。相关研究结果于2016年4月13日在线发表在Cell期刊上,论文标题为“Rapid inflammasome activation following mucosal SIV infection of rhesus monkeys”。
论文第一作者兼论文通信作者、贝斯以色列女执事医疗中心(Beth Israel Deaconess Medical Center, BIDMC)病毒学与疫苗研究中心主任、哈佛医学院医学教授Dan Barouch博士说,“在接触到这种病毒头几天期间在血液中初始检测到病毒之前发生的事件在决定这种感染过程中起着至关重要的作用,但是基本上不可能在人体中研究这段时间。我们的研究是迄今为止对HIV / SIV急性感染最为全面的评估。”
这项研究是作为获得美国国家卫生研究院资助的艾滋病疫苗研究协会(Consortium for AIDS Vaccine Research)研究的一部分启动的,而且涉及多家合作的实验室,包括美国凯斯西储大学Rafick-Pierre Sekaly博士领导的研究团队和弗雷德里克国家癌症研究实验室Jeffrey Lifson博士领导的研究团队。
作者: ipsvirus 时间: 2016-12-12 20:03 Rapid inflammasome activation following mucosal SIV infection of rhesus monkeys
Dan H. Barouch, Khader Ghneim, William J. Bosche, Yuan Li, Brian Berkemeier, Michael Hull, Sanghamitra Bhattacharyya, Mark Cameron, Jinyan Liu, Kaitlin Smith, Erica Borducchi, Crystal Cabral, Lauren Peter, Amanda Brinkman, Mayuri Shetty, Hualin Li, Courtney Gittens, Chantelle Baker, Wendeline Wagner, Mark G. Lewis, Arnaud Colantonio, Hyung-Joo Kang, Wenjun Li, Jeffrey D. Lifson, Michael Piatak Jr., Rafick-Pierre Sekaly
The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-β pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.