Human immunodeficiency virus type-1 infection inhibits autophagy

AIDS. 2008 Mar 30;22(6):695-9. doi: 10.1097/QAD.0b013e3282f4a836.


Objectives: Human immunodeficiency virus type-1 (HIV-1) induces a series of alterations in the host cell that modify the intracellular environment in favor of viral replication, survival and spread. This research examined the impact of HIV-1 infection on autophagy in HIV-1 infected cells.

Methods: Protein extracts of HIV-1 infected and control CD4+ T-lymphocytes and U937 cells were semi-quantified by western blot. The autophagy-related protein Beclin 1, a Bcl-2 associated protein, and the 16 kD microtubule-associated protein (MAP) light chain three (LC3) which is essential for autophagy were quantified and validated using the intracellular protein GAPDH as an internal standard. Beclin 1 mRNA was quantified by real-time reverse transcriptase-polymerase chain reaction. Autophagosomes were assessed by visualization under confocal microscopy following intracellular staining of the LC3 protein.

Results: Following infection of human peripheral blood CD4+ T-cells or U937 cells with HIV-1 for 48 h, the autophagy protein Beclin 1 and LC3 II, which is essential for autophagy, were found to be markedly decreased. Beclin 1 mRNA expression was also reduced. Autophagosomes were reduced in HIV-1-infected cells. The reduction of autophagic protein expression and autophagosomes in HIV-1-infected cells could be overcome by amino acid starvation or rapamycin.

Conclusions: These data demonstrate that HIV-1 infection can down-regulate autophagy in infected cells during acute infection, and provide new insights into HIV-1-induced cell death and disease-related pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Amino Acids / metabolism
  • Apoptosis Regulatory Proteins / analysis
  • Apoptosis Regulatory Proteins / genetics
  • Autophagy*
  • Beclin-1
  • Biomarkers / analysis
  • CD4-Positive T-Lymphocytes / pathology*
  • Cell Line
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Microscopy, Confocal
  • Microtubule-Associated Proteins / analysis
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sirolimus / therapeutic use
  • Virus Replication


  • Amino Acids
  • Apoptosis Regulatory Proteins
  • BECN1 protein, human
  • Beclin-1
  • Biomarkers
  • Immunosuppressive Agents
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • RNA, Messenger
  • Sirolimus