Essential Role of Human T Cell Leukemia Virus Type 1 orf-I in Lethal Proliferation of CD4 + Cells in Humanized Mice

Author:

Galli Veronica1,Nixon Christopher C.2,Strbo Natasa3,Artesi Maria45,de Castro-Amarante Maria F.1,McKinnon Katherine6,Fujikawa Dai1,Omsland Maria1,Washington-Parks Robyn1,Romero Laura3,Caruso Breanna7,Durkin Keith45,Brown Sophia6,Karim Baktiar8,Vaccari Monica1,Jacobson Steve7,Zack Jerome A.2,Van den Broeke Anne45,Pise-Masison Cynthia1,Franchini Genoveffa1

Affiliation:

1. Animal Models and Retroviral Vaccines Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

2. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA

3. Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA

4. Laboratory of Experimental Hematology, Jules Bordet Institute, Free University of Brussels, Brussels, Belgium

5. Unit of Animal Genomics, GIGA, University of Liège, Liège, Belgium

6. Vaccine Branch Flow Cytometry Core, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

7. Viral Immunology Section, Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

8. Pathology/Histotechnology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA

Abstract

Humanized mice constitute a useful model for studying the HTLV-1-associated polyclonal proliferation of CD4 + T cells and viral integration sites in the human genome. The rapid death of infected animals, however, appears to preclude the clonal selection typically observed in human ATLL, which normally develops in 2 to 5% of individuals infected with HTLV-1. Nevertheless, the expansion of multiple clones of low abundance in these humanized mice mirrors the early phase of HTLV-1 infection in humans, providing a useful model to investigate approaches to inhibit virus-induced CD4 + T cell proliferation.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | Office of AIDS Research

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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