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Updated: Feb 24, 2026

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HIV-1 Nef-induced cardiotoxicity through dysregulation of autophagy

Manish K Gupta1, Rafal Kaminski1, Brian Mullen1

  • 1Department of Neuroscience, Center for Neurovirology and Comprehensive NeuroAIDS Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.

Scientific Reports
|August 19, 2017
PubMed

Insights

HIV-1 Nef protein impairs cardiomyocyte health by disrupting autophagy, a key cellular cleaning process. This dysfunction contributes to heart disease in HIV patients, but rapamycin treatment showed promise in reversing these effects.

Area of Science:

  • Cardiovascular Biology
  • Virology
  • Cellular Biology

Background:

  • Cardiovascular disease is a major complication in HIV-1 patients, irrespective of viral load.
  • The exact cause of HIV-1-associated cardiomyopathy remains unclear, with no direct viral replication in heart cells.
  • Extracellular release of HIV-1 Nef protein from infected CD4+ T cells is suspected to impact heart tissue.

Purpose of the Study:

  • To investigate the impact of HIV-1 Nef on protein quality control (PQC) and autophagy in cardiomyocytes.
  • To understand the molecular mechanisms by which Nef affects cardiomyocyte homeostasis.

Main Methods:

  • Detection of Nef in patient serum and heart tissue.
  • Cell and molecular biology techniques to study Nef's effects on cardiomyocytes.
  • Analysis of PQC pathways and autophagy flux, including interactions with Beclin 1/Rab7 and TFEB localization.

Main Results:

  • HIV-1 Nef inhibits autophagy flux, leading to cardiomyocyte cytotoxicity and death.
  • Nef interferes with autophagosome maturation by affecting Beclin 1/Rab7 interactions and TFEB-mediated lysosome regulation.
  • Rapamycin treatment successfully reversed the detrimental effects of Nef on cardiomyocytes.

Conclusions:

  • HIV-1 Nef-induced inhibition of cellular PQC and autophagy is a potential mechanism driving HIV-associated cardiomyopathy.
  • Targeting autophagy may offer a therapeutic strategy for managing heart disease in HIV-1 patients.

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