Cell death is counteracted by mitophagy in HIV2 productively infected astrocytes but is promoted by 3 inflammasome activation among non-productively infected 4 cells

AUTHORS: DIEGO OJEDA1, DANIEL GRASSO2, JAVIER URQUIZA1, ANDREAS TILL3,47 , MARÍA INÉS VACCARO2 AND JORGE QUARLERI; AUTHORS: DIEGO OJEDA1, DANIEL GRASSO2, JAVIER URQUIZA1, ANDREAS TILL3,47 , MARÍA INÉS VACCARO2 AND JORGE QUARLERI

Frontiers in immunology

Frontiers media SA

Lugar: Londres; Año: 2018 vol. 9 p. 101 - 119

1664-3224

Frontiers Immunology Editorial Office <immunology.editorial.office@frontiersin.org>Thu, Oct 25, 2018 at 7:13 AMReply-To: Frontiers Immunology Editorial Office <immunology.editorial.office@frontiersin.org>To: mvaccaro@ffyb.uba.arDear Dr Vaccaro, I am pleased to inform you that your manuscript Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells has been approved for production and accepted for publication in Frontiers in Immunology, section Viral Immunology. Manuscript title: Cell death is counteracted by mitophagy in HIV-productively infected astrocytes but is promoted by inflammasome activation among non-productively infected cells Journal: Frontiers in Immunology, section Viral ImmunologyArticle type: Original ResearchAuthors:  Diego Sebastian Ojeda, Daniel Grasso, Javier Urquiza, Andreas Till, Maria Ines Vaccaro, Jorge QuarleriManuscript ID: 395694Edited by: Shokrollah Elahi2 Despite more than 30 years of extensive research efforts, a complete understanding3 of the neurological consequences of HIV central nervous system (CNS) infection4 remains elusive. HIV is not only able to establish a viral reservoir in the CNS but5 also to initiate manifestation of neurodegenerative diseases. These neurological6 disorders may arise because of virus-induced activation of the inflammasome in CNS7 cells, including astrocytes. Nevertheless, in some productive viral infection8 scenarios, selective autophagy may reduce inflammation through mitochondrial9 degradation (?mitophagy‟) to counteract inflammasome activation. In this study,10 using cultured human astrocytes, we demonstrate that - depending on the HIV11 infection outcome - cells may resist death, or succumb by inflammasome activation12 when viral infection is productive or abortive, respectively. Cells productively13 infected with HIV were able to attenuate both mitochondrial ROS production and14 mitochondrial membrane potential dissipation, thus exhibiting cell death resistance.15 Interestingly, mitochondrial injury was counteracted by increasing the autophagic16 flux and by activating mitophagy. Conversely, astrocytes exposed to HIV in an17 abortive scenario showed prominent mitochondrial damage, inflammasome18 activation, and cell death. This bystander effect occurred after cell-to-cell contact19 with HIV-productively infected astrocytes. In summary, we demonstrate a tight20 functional crosstalk between viral infection mode, inflammasome activation,21 autophagy pathways and cell fate in the context of HIV infection. Moreover,22 mitophagy is crucial for cell death resistance in HIV-productively infected23 astrocytes, but its impairment may favor inflammasome-mediated cell death in24 abortively infected cells.#s3gt_translate_tooltip_mini { display: none !important; }