Evidence map›Paper›PMID 22647372›Full record

ArticleThe Journal of general virology2012

A doxycycline-dependent human immunodeficiency virus type 1 replicates in vivo without inducing CD4+ T-cell depletion.

Nicolas Legrand, Gisela J van der Velden, Raphaël Ho Tsong Fang, Marc Douaisi, Kees Weijer, Atze T Das, Bianca Blom, Christel H Uittenbogaart, Ben Berkhout, Mireille Centlivre

Abstract read
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In one paragraph

Article in The Journal of general virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Nicolas LegrandDepartment of Cell Biology and Histology, Center for Immunology of Amsterdam (CIA), Academic Medical Center of the University of Amsterdam (AMC-UvA), Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Gisela J van der VeldenLaboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam (AMC-UvA), Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Raphaël Ho Tsong FangMicrobiology, Immunology and Molecular Genetics, and Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
Marc DouaisiMicrobiology, Immunology and Molecular Genetics, and Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
Kees WeijerDepartment of Cell Biology and Histology, Center for Immunology of Amsterdam (CIA), Academic Medical Center of the University of Amsterdam (AMC-UvA), Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Atze T DasLaboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam (AMC-UvA), Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Bianca BlomDepartment of Cell Biology and Histology, Center for Immunology of Amsterdam (CIA), Academic Medical Center of the University of Amsterdam (AMC-UvA), Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Christel H UittenbogaartMicrobiology, Immunology and Molecular Genetics, and Pediatrics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California, USA.
Ben BerkhoutDepartment of Cell Biology and Histology, Center for Immunology of Amsterdam (CIA), Academic Medical Center of the University of Amsterdam (AMC-UvA), Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Mireille CentlivreLaboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam (AMC-UvA), Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.

Funding

Conditional live HIV-1 variant to study immune activation and pathogenesis.R21AI073136 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI UITTENBOGAART, CHRISTEL H. · 2007 to 2008
$402k
NIAID NIH HHS R21 AI073136NIAID NIH HHS R21-AI073136
6 · The paper itself

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.

Indexed as

Gene Expression Regulation, ViralVirus ReplicationAnimalsCD4-Positive T-LymphocytesCells, CulturedDoxycyclineHIV-1HIV InfectionsHumansLymphocyte DepletionMiceMice, Inbred BALB CMice, KnockoutDoxycycline

Identifiers

PMID22647372
PMCPMC3542129

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.