title: Dynamics of HIV latency and reactivation in a primary CD4+ T cell model.
abstract: HIV latency is a major obstacle to curing infection. Current strategies to eradicate HIV aim at increasing transcription of the latent provirus. In the present study we observed that latently infected CD4+ T cells from HIV-infected individuals failed to produce viral particles upon ex vivo exposure to SAHA (vorinostat), despite effective inhibition of histone deacetylases. To identify steps that were not susceptible to the action of SAHA or other latency reverting agents, we used a primary CD4+ T cell model, joint host and viral RNA sequencing, and a viral-encoded reporter. This model served to investigate the characteristics of latently infected cells, the dynamics of HIV latency, and the process of reactivation induced by various stimuli. During latency, we observed persistence of viral transcripts but only limited viral translation. Similarly, the reactivating agents SAHA and disulfiram successfully increased viral transcription, but failed to effectively enhance viral translation, mirroring the ex vivo data. This study highlights the importance of post-transcriptional blocks as one mechanism leading to HIV latency that needs to be relieved in order to purge the viral reservoir.
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel and Lausanne, Switzerland.
authors.forename: Pejman
authors.initials: P
authors.lastname: Mohammadi
authors.affiliation: Swiss Institute of Bioinformatics, Basel and Lausanne, Switzerland; Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Julia
authors.initials: J
authors.lastname: di Iulio
authors.affiliation: Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Raquel
authors.initials: R
authors.lastname: Martinez
authors.affiliation: Swiss Institute of Bioinformatics, Basel and Lausanne, Switzerland; Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: István
authors.initials: I
authors.lastname: Bartha
authors.affiliation: Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.affiliation: Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Thorball
authors.affiliation: Swiss Institute of Bioinformatics, Basel and Lausanne, Switzerland; Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Jacques
authors.initials: J
authors.lastname: Fellay
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland; Swiss Institute of Bioinformatics, Basel and Lausanne, Switzerland.
authors.forename: Niko
authors.initials: N
authors.lastname: Beerenwinkel
authors.affiliation: Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; University of Lausanne, Lausanne, Switzerland.
authors.forename: Angela
authors.initials: A
authors.lastname: Ciuffi
authors.affiliation: Institute of Microbiology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; University of Lausanne, Lausanne, Switzerland.
authors.forename: Amalio
authors.initials: A
authors.lastname: Telenti
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1; D006801:Humans; D018448:Models, Immunological; D012367:RNA, Viral / Q000235:genetics; D016662:Virus Integration / Q000235:genetics; D017735:Virus Latency / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
chemical_list: D012367:RNA, Viral