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Human immunodeficiency virus type-1 infection inhibits autophagy

Zhou, Dejianga; Spector, Stephen Aa,b,c

doi: 10.1097/QAD.0b013e3282f4a836
Basic Science: Concise Communication

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.

From the aDepartment of Pediatrics, Division of Infectious Diseases, USA

bCenter for Molecular Genetics, USA

cCenter for AIDS Research, University of California San Diego, La Jolla, California, 92093-0672, USA.

Received 18 July, 2007

Revised 30 October, 2007

Accepted 13 November, 2007

Correspondence to Stephen A. Spector, MD, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0672, USA. E-mail: saspector@ucsd.edu

© 2008 Lippincott Williams & Wilkins, Inc.