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  • Oral presentation
  • Open Access

Human immunodeficiency virus impairs reverse cholesterol transport from macrophages

  • 1,
  • 1,
  • 2 and
  • 1
Retrovirology20063 (Suppl 1) :S82

https://doi.org/10.1186/1742-4690-3-S1-S82

  • Published:

Keywords

  • Cholesterol
  • Plasma Membrane
  • Atherosclerosis
  • Human Immunodeficiency Virus
  • Infectious Disease

We demonstrate that HIV-1, via Nef, impairs ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux from human macrophages. At least two mechanisms were involved: first, HIV infection and transfection with Nef induced post-transcriptional down-regulation of ABCA1; and second, Nef caused redistribution of ABCA1 to the plasma membrane and inhibited internalization of apolipoprotein A-I. Binding of Nef to ABCA1 was required for down-regulation and redistribution of ABCA1. Stimulation of cholesterol efflux from macrophages reduced infectivity of produced virions, and this effect correlated with a decreased amount of virion-associated cholesterol. Therefore, impairment of cholesterol efflux is essential to viral replication as it ensures proper cholesterol content in nascent HIV particles. This impairment may be a contributing factor to atherosclerosis in HIV patients.

Authors’ Affiliations

(1)
Department of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, District of Columbia 20037, USA
(2)
Baker Heart Research Institute, Melbourne, Victoria, 8008, Australia

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