Human immunodeficiency virus type-1 infection inhibits autophagy.
OBJECTIVE
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.
Zhou
Dejiang
D
Department of Pediatrics, Division of Infectious Diseases, University of California San Diego, La Jolla, California, 92093-0672, USA.
Spector
Stephen A
SA
D000208:Acute Disease; D000596:Amino Acids / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics; D001343:Autophagy; D000071186:Beclin-1; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D002460:Cell Line; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000627:therapeutic use; D014779:Virus Replication
D000596:Amino Acids; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D015415:Biomarkers; D007166:Immunosuppressive Agents; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D020123:Sirolimus