title: Inhibition of HIV-1 replication with stable RNAi-mediated knockdown of autophagy factors.
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.
authors.affiliation: 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.
authors.forename: Julia Jm
authors.initials: JJ
authors.lastname: Eekels
authors.forename: Sophie
authors.initials: S
authors.lastname: Sagnier
authors.forename: Dirk
authors.initials: D
authors.lastname: Geerts
authors.forename: Rienk E
authors.initials: RE
authors.lastname: Jeeninga
authors.forename: Martine
authors.initials: M
authors.lastname: Biard-Piechaczyk
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D001343:Autophagy; D002460:Cell Line; D002470:Cell Survival; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication