Nardacci Roberta, Amendola Alessandra, Ciccosanti Fabiola, Corazzari Marco, Esposito Valentina, Vlassi Chrysoula, Taibi Chiara, Fimia Gian Maria, Del Nonno Franca, Ippolito Giuseppe, D'Offizi Gianpiero, Piacentini Mauro
National Institute for Infectious Diseases; IRCCS "L. Spallanzani"; Rome, Italy.
National Institute for Infectious Diseases; IRCCS "L. Spallanzani"; Rome, Italy; Department of Biology; University of Rome "Tor Vergata"; Rome, Italy.
Autophagy. 2014 Jul;10(7):1167-78. doi: 10.4161/auto.28678. Epub 2014 Apr 29.
Recent in vitro studies have suggested that autophagy may play a role in both HIV-1 replication and disease progression. In this study we investigated whether autophagy protects the small proportion of HIV-1 infected individuals who remain clinically stable for years in the absence of antiretroviral therapy, these named long-term nonprogressors (LTNP) and elite controllers (EC). We found that peripheral blood mononuclear cells (PBMC) of the HIV-1 controllers present a significantly higher amount of autophagic vesicles associated with an increased expression of autophagic markers with respect to normal progressors. Of note, ex vivo treatment of PBMC from the HIV-1 controllers with the MTOR inhibitor rapamycin results in a more efficient autophagic response, leading to a reduced viral production. These data lead us to propose that autophagy contributes to limiting viral pathogenesis in HIV-1 controllers by targeting viral components for degradation.
最近的体外研究表明，自噬可能在HIV-1复制和疾病进展中都发挥作用。在本研究中，我们调查了自噬是否对一小部分在没有抗逆转录病毒治疗的情况下多年保持临床稳定的HIV-1感染者起到保护作用，这些人被称为长期不进展者（LTNP）和精英控制者（EC）。我们发现，与正常进展者相比，HIV-1控制者的外周血单核细胞（PBMC）呈现出显著更多的自噬囊泡，且自噬标志物的表达增加。值得注意的是，用mTOR抑制剂雷帕霉素对HIV-1控制者的PBMC进行离体处理会导致更有效的自噬反应，从而使病毒产生减少。这些数据使我们提出，自噬通过靶向病毒成分进行降解，有助于限制HIV-1控制者的病毒发病机制。
