An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rgammanull mice allows HIV replication and development of anti-HIV immune responses.

Singh, Maneesh; Singh, Pratibha; Gaudray, Gilles; Musumeci, Lucia; Thielen, Caroline; VAIRA, Dolorès; Vandergeeten, Claire; Delacroix, Laurence; Van Gulck, Ellen; Vanham, Guido; de Leval, Laurence; Rahmouni, Souad; MOUTSCHEN, Michel

doi:10.1371/journal.pone.0038491

Article (Scientific journals)

An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rgammanull mice allows HIV replication and development of anti-HIV immune responses.

Singh, Maneesh; Singh, Pratibha; Gaudray, Gilles et al.

2012 • In PLoS ONE, 7 (6), p. 38491

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/126403

DOI
10.1371/journal.pone.0038491

PubMed
22675567

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Keywords :

Animals; Antigens, CD34/metabolism; Antigens, CD45/metabolism; Cell Differentiation/immunology; Cell Lineage; Cell Proliferation; Cord Blood Stem Cell Transplantation/methods; Disease Progression; HIV/immunology/physiology; HIV Infections/immunology/pathology/virology; Hematopoietic Stem Cells/metabolism; Humans; Immunity/immunology; Interleukin Receptor Common gamma Subunit/deficiency/immunology; Lymphoid Tissue/immunology; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Receptors, Antigen, T-Cell/metabolism; Receptors, CCR5/metabolism; Receptors, CXCR4/metabolism; T-Lymphocytes/immunology/pathology/virology; Virus Replication/immunology

Abstract :

[en] Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rgamma(null) (NSG) and NOD/SCID/IL2Rgamma(null) (NOG) mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI) is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials.

Disciplines :

Immunology & infectious disease

Author, co-author :

Singh, Maneesh

Singh, Pratibha

Gaudray, Gilles

Musumeci, Lucia ; Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.

Thielen, Caroline ; Université de Liège - ULiège > GIGA - Neurosciences

VAIRA, Dolorès

Vandergeeten, Claire

Delacroix, Laurence ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques

Van Gulck, Ellen

Vanham, Guido

More authors (3 more)

Language :

English

Title :

An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rgammanull mice allows HIV replication and development of anti-HIV immune responses.

Publication date :

2012

Journal title :

PLoS ONE

eISSN :

1932-6203

Publisher :

Public Library of Science, San Franscisco, United States

Volume :

Issue :

Pages :

e38491

Peer reviewed :

Peer Reviewed verified by ORBi

Funders :

PAI

Available on ORBi :

since 27 June 2012

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