HIV-1 cellular and tissue replication patterns in infected humanized mice

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Abstract

Humanized mice have emerged as a testing platform for HIV-1 pathobiology by reflecting natural human disease processes. Their use to study HIV-1 biology, virology, immunology, pathogenesis and therapeutic development has served as a robust alternative to more-well developed animal models for HIV/AIDS. A critical component in reflecting such human pathobiology rests in defining the tissue and cellular sites for HIV-1 infection. To this end, we examined the tissue sites for viral infection in bone marrow, blood, spleens, liver, gut, brain, kidney and lungs of human CD34+ hematopoietic stem cell engrafted virus-infected NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Cells were analyzed by flow cytometry and sorted from species mixtures defined as CD34+ lineage negative progenitor cells, CD14+CD16+ monocyte-macrophages and central, stem cell and effector memory T cells. The cell distribution and viral life cycle were found dependent on the tissue compartment and time of infection. Cell subsets contained HIV-1 total and integrated DNA as well as multi-spliced and unspliced RNA in divergent proportions. The data support the idea that humanized mice can provide a means to examine the multifaceted sites of HIV-1 replication including, but not limited to progenitor cells and monocyte-macrophages previously possible only in macaques and human.

Original languageEnglish (US)
Article number23513
JournalScientific reports
Volume6
DOIs
StatePublished - Mar 21 2016

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HIV-1
Stem Cells
Monocyte-Macrophage Precursor Cells
Virology
Macaca
Virus Diseases
Hematopoietic Stem Cells
Allergy and Immunology
Life Cycle Stages
HIV Infections
Monocytes
Flow Cytometry
Acquired Immunodeficiency Syndrome
Spleen
Animal Models
Bone Marrow
Macrophages
HIV
RNA
Viruses

ASJC Scopus subject areas

  • General

Cite this

HIV-1 cellular and tissue replication patterns in infected humanized mice. / Araínga, Mariluz; Su, Hang; Poluektova, Larisa Y; Gorantla, Santhi; Gendelman, Howard Eliot.

In: Scientific reports, Vol. 6, 23513, 21.03.2016.

Research output: Contribution to journalArticle

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