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摘要 : 美国哈佛大学医学院等处的研究人员发现,在恒河猴感染“猿免疫缺陷病毒”之后最早三天内,给猴子抗病毒治疗并不能阻止病毒复制的后续反弹,这表明病毒库在早期就已经成立了。相关文章发表于2014年7月20日的《Nature》杂志上。



Dan Barouch及同事在一个猴子模型中对这些库的形成时机进行了研究。他们发现,在恒河猴感染“猿免疫缺陷病毒”之后最早三天内、在病毒血症产生之前所进行的抗病毒治疗未能防止病毒库的形成,当药物治疗中断时病毒最终会反弹。


Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys

James B. Whitney, Alison L. Hill, Srisowmya Sanisetty, Pablo Penaloza-MacMaster, Jinyan Liu, Mayuri Shetty, Lily Parenteau, Crystal Cabral, Jennifer Shields, Stephen Blackmore,Jeffrey Y. Smith, Amanda L. Brinkman, Lauren E. Peter, Sheeba I. Mathew, Kaitlin M. Smith,Erica N. Borducchi, Daniel I. S. Rosenbloom, Mark G. Lewis, Jillian Hattersley, Bei Li,Joseph Hesselgesser, Romas Geleziunas, Merlin L. Robb, Jerome H. Kim, Nelson L. Michael et al.

The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (HIV-1) eradication strategies. However, it remains unclear when and wher the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before systemic viraemia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIVMAC251infection. Treatment with ART on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later time points. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, after discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound as compared with those treated on days 7, 10 and 14. The time to viral rebound correlated with total viraemia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the ‘eclipse’ phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies.

对应Nature杂志: 2014年8月7日Nature杂志精选

来源: Nature 浏览次数:96


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