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Open Access Highly Accessed Research

Inhibition of HIV-1 replication with stable RNAi-mediated knockdown of autophagy factors

Julia JM Eekels1, Sophie Sagnier2, Dirk Geerts34, Rienk E Jeeninga1, Martine Biard-Piechaczyk2 and Ben Berkhout1*

Author Affiliations

1 Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105, AZ Amsterdam, The Netherlands

2 Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, CPBS UMR5236 CNRS UMSF, 1919 Route de Mende, 34293 Montpellier, France

3 Department of Human Genetics, Academic Medical Center of the University of Amsterdam, Meibergdreef 15, 1105, AZ Amsterdam, The Netherlands

4 Department of Pediatric Oncology/Hematology, Sophia Children's Hospital, Erasmus University Medical Center, Dr. Molewaterplein 60, 3015, GJ Rotterdam, The Netherlands

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Virology Journal 2012, 9:69  doi:10.1186/1743-422X-9-69

Published: 16 March 2012

Abstract

Autophagy is a cellular process leading to the degradation of cytoplasmic components such as organelles and intracellular pathogens. It has been shown that HIV-1 relies on several components of the autophagy pathway for its replication, but the virus also blocks late steps of autophagy to prevent its degradation. We generated stable knockdown T cell lines for 12 autophagy factors and analyzed the impact on HIV-1 replication. RNAi-mediated knockdown of 5 autophagy factors resulted in inhibition of HIV-1 replication. Autophagy analysis confirmed a specific defect in the autophagy pathway for 4 of these 5 factors. We also scored the impact on cell viability, but no gross effects were observed. Upon simultaneous knockdown of 2 autophagy factors (Atg16 and Atg5), an additive inhibitory effect was scored on HIV-1 replication. Stable knockdown of several autophagy factors inhibit HIV-1 replication without any apparent cytotoxicity. We therefore propose that targeting of the autophagy pathway can be a novel therapeutic approach against HIV-1

Keywords:
HIV-1; Autophagy; RNAi; Antiviral