Autophagy plays an important role in the containment of HIV-1 in nonprogressor-infected patients

Abstract

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.

Keywords: :

• HIV-1
• autophagy
• long-term nonprogressors
• elite controllers
• cell death
• AMBRA1
• BECN1
• ATG5

Disclosure of Potential Conflict of interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank Dr Marie-Lise Gougeon (Institute Pasteur, Paris, France) and Dr Jean-Luc Perfettini (Institut Gustave Roussy, Villejuif, France) for stimulating discussions and for the kind gift of the anti-gp41 and anti-gp120 antibodies. We thank the U.O.C. Microbiologia e Banca Biologica (National Institute for Infectious Diseases, IRCCS “L. Spallanzani” Rome) for the recruitment of patient samples and Alessia Brenna, Mario Moauro, and Diletta Collalto for technical assistance. A special thanks to the patients enrolled in this study, for their availability and participation. This work was supported by grants from the Ministry for Health of Italy to MP (“Ricerca Corrente” and Ricerca AIDS RF-IMI-2009-1303225) and the Italian Ministry of University and Research (FIRB 2011).