Human Immunodeficiency Virus Type 1 gp120 and Tat Induce Mitochondrial Fragmentation and Incomplete Mitophagy in Human Neurons

Author:

Teodorof-Diedrich Carmen1,Spector Stephen A.12

Affiliation:

1. Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, California, USA

2. Rady Children's Hospital, San Diego, California, USA

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute on Drug Abuse

HHS | NIH | National Institute of Neurological Disorders and Stroke

HHS | NIH | National Institute of Mental Health

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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