Evidence map›Paper›PMID 23691059›Full record

ArticlePloS one2013

Mice transgenic for CD4-specific human CD4, CCR5 and cyclin T1 expression: a new model for investigating HIV-1 transmission and treatment efficacy.

Kieran Seay, Xiaohua Qi, Jian Hua Zheng, Cong Zhang, Ken Chen, Monica Dutta, Kathryn Deneroff, Christina Ochsenbauer, John C Kappes, Dan R Littman and 1 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
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

25 citing papers in PubMed, 37 citations in OpenAlex.

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  8. μ-Lat: A mouse model to evaluate human immunodeficiency virus eradication strategies.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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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

11 authors at 4 institutions in 1 country.

Kieran SeayDepartment of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Xiaohua Qi
Jian Hua Zheng
Cong Zhang
Ken Chen
Monica Dutta
Kathryn Deneroff
Christina Ochsenbauer
John C Kappes
Dan R Littman
Harris Goldstein
Albert Einstein College of Medicine · USBirmingham VA Medical Center · USHoward Hughes Medical Institute · USUniversity of Alabama at Birmingham · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI THOMAS E ROHAN · 1985 to 2026
$111.2M
Virology CoreP30AI027767 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI OLAF KUTSCH · 1988 to 2026
$84.1M
The NYSGRC: A Large Scale Center for PSI:BiologyU54GM094662 · NIGMS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI ALMO, STEVEN C. · 2010 to 2014
$32.6M
Immunology/Pathology CoreP30AI051519 · NIAID · YESHIVA UNIVERSITY · PI GOLDSTEIN, HARRIS · 2003 to 2013
$18.6M
Viral and Host Determinants of HIV-1 TransmissionU01AI067854 · NIAID · DUKE UNIVERSITY · PI HAHN, BEATRICE H · 2005 to 2005
$14.9M
Training in HIV/AIDS Pathogenesis; Basic and Translational ResearchT32AI007501 · NIAID · YESHIVA UNIVERSITY · PI PRASAD, VINAYAKA R. · 1995 to 2024
$6.6M
Consortia for High-Throughput-Enabled Structural Biology Partnerships (U01)U01GM094665 · NIGMS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI CASADEVALL, ARTURO · 2010 to 2014
$5.5M
Impact of HSV-2 on Female Genital Tract Mucosal Immunity & HIV InfectionR01AI065309 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HEROLD, BETSY C. · 2005 to 2014
$5.1M
Systems biology analysis of in vivo impact of substance abuse on HIV infectionR01DA033788 · NIDA · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI GOLDSTEIN, HARRIS · 2012 to 2016
$3.0M
NCI NIH HHS P30 CA013330NCI NIH HHS P30-CA-013330NIAID NIH HHS AI51519NIAID NIH HHS P30 AI027767NIAID NIH HHS P30 AI051519NIAID NIH HHS P30-AI-27767NIAID NIH HHS R01 AI065309NIAID NIH HHS R01-AI065309NIAID NIH HHS T32 AI007501NIAID NIH HHS T32-AI007501NIAID NIH HHS U01 AI067854NIAID NIH HHS U01-AI067854NIDA NIH HHS R01 DA033788NIDA NIH HHS R01-DA-033788NIGMS NIH HHS U01 GM094665NIGMS NIH HHS U01-GM-094665NIGMS NIH HHS U54 GM094662NIGMS NIH HHS U54-GM-094662
6 · The paper itself

Abstract

Mice cannot be used to evaluate HIV-1 therapeutics and vaccines because they are not infectible by HIV-1 due to structural differences between several human and mouse proteins required for HIV-1 entry and replication including CD4, CCR5 and cyclin T1. We overcame this limitation by constructing mice with CD4 enhancer/promoter-regulated human CD4, CCR5 and cyclin T1 genes integrated as tightly linked transgenes (hCD4/R5/cT1 mice) promoting their efficient co-transmission and enabling the murine CD4-expressing cells to support HIV-1 entry and Tat-mediated LTR transcription. All of the hCD4/R5/cT1 mice developed disseminated infection of tissues that included the spleen, small intestine, lymph nodes and lungs after intravenous injection with an HIV-1 infectious molecular clone (HIV-IMC) expressing Renilla reniformis luciferase (LucR). Furthermore, localized infection of cervical-vaginal mucosal leukocytes developed after intravaginal inoculation of hCD4/R5/cT1 mice with the LucR-expressing HIV-IMC. hCD4/R5/cT1 mice reproducibly developed in vivo infection after inoculation with LucR-expressing HIV-IMC which could be bioluminescently quantified and visualized with a high sensitivity and specificity which enabled them to be used to evaluate the efficacy of HIV-1 therapeutics. Treatment with highly active anti-retroviral therapy or one dose of VRC01, a broadly neutralizing anti-HIV-1 antibody, almost completed inhibited acute systemic HIV-1 infection of the hCD4/R5/cT1 mice. hCD4/R5/cT1 mice could also be used to evaluate the capacity of therapies delivered by gene therapy to inhibit in vivo HIV infection. VRC01 secreted in vivo by primary B cells transduced with a VRC01-encoding lentivirus transplanted into hCD4/R5/cT1 mice markedly inhibited infection after intravenous challenge with LucR-expressing HIV-IMC. The reproducible infection of CD4/R5/cT1 mice with LucR-expressing HIV-IMC after intravenous or mucosal inoculation combined with the availability of LucR-expressing HIV-IMC expressing transmitted/founder and clade A/E and C Envs will provide researchers with a highly accessible pre-clinical in vivo HIV-1-infection model to study HIV-1 acquisition, treatment, and prevention.

Indexed as

Models, BiologicalAnimalsAntiretroviral Therapy, Highly ActiveBase SequenceCD4 AntigensCD4-Positive T-LymphocytesCyclin TDNA PrimersFlow CytometryHIV-1HIV InfectionsHumansMiceMice, TransgenicReceptors, CCR5CCR5 protein, humanCD4 AntigensCyclin TDNA PrimersReceptors, CCR5

Identifiers

PMID23691059
PMCPMC3655194
OpenAlexW2082354489

What OpenQuestion holds

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LicenceCC BY
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.