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Journal of General Virology header logo Journal of General Virology

Volume 93, Issue 9

A doxycycline-dependent human immunodeficiency virus type 1 replicates without inducing CD4 T-cell depletion No Access

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 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 . These results demonstrate the proof of concept that HIV-rtTA replicates efficiently . HIV-rtTA is a promising tool for fundamental research to study virus–host interactions in a controlled fashion.

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© 2012 SGM
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2012-09-01
2025-12-11

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A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion
J. Gen. Virol. 93, 2017 (2012); https://doi.org/10.1099/vir.0.042796-0
/content/journal/jgv/10.1099/vir.0.042796-0
/content/journal/jgv/10.1099/vir.0.042796-0
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