@article{mbs:/content/journal/jgv/10.1099/vir.0.042796-0, author = "Legrand, Nicolas and van der Velden, Gisela J. and Fang, Raphaël Ho Tsong and Douaisi, Marc and Weijer, Kees and Das, Atze T. and Blom, Bianca and Uittenbogaart, Christel H. and Berkhout, Ben and Centlivre, Mireille", title = "A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion", journal= "Journal of General Virology", year = "2012", volume = "93", number = "9", pages = "2017-2027", doi = "https://doi.org/10.1099/vir.0.042796-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.042796-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "A novel genetic approach for the control of virus replication was used for the design of a conditionally replicating human immunodeficiency virus (HIV) variant, HIV-rtTA. HIV-rtTA gene expression and virus replication are strictly dependent on the presence of a non-toxic effector molecule, doxycycline (dox), and thus can be turned on and off at will in a graded and reversible manner. The in vivo replication capacity, pathogenicity and genetic stability of this HIV-rtTA variant were evaluated in a humanized mouse model of haematopoiesis that harbours lymphoid and myeloid components of the human immune system (HIS). Infection of dox-fed BALB Rag/γc HIS (BRG-HIS) mice with HIV-rtTA led to the establishment of a productive infection without CD4+ T-cell depletion. The virus did not show any sign of escape from dox control for up to 10 weeks after the onset of infection. No reversion towards a functional Tat–transactivating responsive (TAR) RNA element axis was observed, confirming the genetic stability of the HIV-rtTA variant in vivo. These results demonstrate the proof of concept that HIV-rtTA replicates efficiently in vivo. HIV-rtTA is a promising tool for fundamental research to study virus–host interactions in vivo in a controlled fashion.", }