Human Immunodeficiency Virus Promotes Mitochondrial Toxicity

Abstract

Combined antiretroviral therapies (cART) have had remarkable success in reducing morbidity and mortality among patients infected with human immunodeficiency virus (HIV). However, mild forms of HIV-associated neurocognitive disorders (HAND), characterized by loss of synapses, remain. cART may maintain an undetectable HIV RNA load but does not eliminate the expression of viral proteins such as trans-activator of transcription (Tat) and the envelope glycoprotein gp120 in the brain. These two viral proteins are known to promote synaptic simplifications by several mechanisms, including alteration of mitochondrial function and dynamics. In this review, we aim to outline the many targets and pathways used by viral proteins to alter mitochondria dynamics, which contribute to HIV-induced neurotoxicity. A better understanding of these pathways is crucial for the development of adjunct therapies for HAND.

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Acknowledgements

This work was supported by HHS grants 1R01 NS079172 to I.M. and T32 NS041218 to S.R.

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Correspondence to Italo Mocchetti.

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Rozzi, S.J., Avdoshina, V., Fields, J.A. et al. Human Immunodeficiency Virus Promotes Mitochondrial Toxicity. Neurotox Res 32, 723–733 (2017). https://doi.org/10.1007/s12640-017-9776-z

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Keywords

  • Ca2+
  • gp120
  • HAND
  • Mitochondria
  • Neurotoxicity
  • Tat