Human Immunodeficiency Virus Type 1 gp120 and Tat Induce Mitochondrial Fragmentation and Incomplete Mitophagy in Human Neurons
Year: 2018
Type: article
Abstract: Despite viral suppression by antiretrovirals, HIV proteins continue to be detected in infected cells and neurologic complications remain common in infected people. Although HIV is unable to infect neurons, viral proteins, including gp120 and Tat, can enter neurons and can cause neuronal degeneration and neurocognitive impairment. Neuronal health is dependent on the functional integrity of mitochondria, and damaged mitochondria are subjected to mitochondrial control mechanisms. Multiple lines of evidence suggest that specific elimination of damaged mitochondria through mitophagy and mitochondrial dynamics play an important role in CNS diseases. Here, we show that in human primary neurons, gp120 and Tat favor the balance of mitochondrial dynamics toward enhanced fragmentation through the activation of mitochondrial translocation of DRP1 to the damaged mitochondria. However, mitophagy fails to go to completion, leading to neuronal damage. These findings support a role for altered mitophagy in HIV-associated neurological disorders and provide novel targets for potential intervention.
Source: Journal of Virology
DOI: 10.1128/jvi.00993-18
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institutes of Health, University of California, San Diego, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Modulating Autophagy to Eradicate HIV-1 from CNS Reservoirs, G1654426238, G2004382792, Translational Methamphetamine AIDS Research Center (TMARC), G2135780636, G2650613164, G3045663399, G3156725562, G3262353703, G3342746445, G3665517470, G4853082081, G5192876114, G5602729146, G7397782118, G7445317512, G803170016, G8500352392, G8922259349, Interdisciplinary Research Fellowship in NeuroAIDS, SDMC - IMPAACT Leadership Group
OpenAlex ID: W2888974375