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.

Autophagy Induction by Histone Deacetylase Inhibitors Inhibits HIV Type 1

“…Further highlighting autophagy in the control of HIV, a recent study found that peripheral blood mononuclear cells from elite controllers contain significantly more autophagic vesicles and express more autophagic markers than normal progressors. Moreover, the same peripheral blood mononuclear cells from elite controllers were more responsive to sirolimus treatment leading to an enhanced autophagic response and a greater reduction in virus production (58). Dissecting the molecular mechanisms by which HIV utilizes autophagy has the potential to lead to the identification of novel drug candidates to treat HIV infection and related opportunistic infections.…”

Viruses and the autophagy pathway

“…(Sagnier et al, 2014) In CD4+ T lymphocytes, autophagy selectively degrades HIV Tat protein, restricting viral replication. (Nardacci et al, 2014) However, it has also been shown that knockdown of autophagy factors in T-cell lines can inhibit HIV replication. (Eekels et al, 2012) Certainly there is a complex relationship between HIV and autophagy, and the nature of the interactions between virus and pathway depend on the cell and the circumstances.…”

Ambra1 at a glance

“…Recently, augmented expression levels of Ambra1 have been found in the peripheral blood mononuclear cells (PBMCs) and lymph nodes of nonprogressor human immunodeficiency virus-1 (HIV-1)-infected individuals, where it contributes to maintaining a robust autophagic response. The sustained autophagy in these individuals is most likely to be responsible for the clinical stability that has been observed in the absence of therapy (Nardacci et al, 2014).…”