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Life Sci Alliance ; 3(8)2020 08.
Article in English | MEDLINE | ID: mdl-32576602

ABSTRACT

HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination, these viruses are linked to AIDS-associated lymphomas. We found that EBV, which transforms B cells, renders them susceptible to HIV-1 infection in a CXCR4 and CD4-dependent manner in vitro and that CXCR4-tropic HIV-1 integrates into the genome of these B cells with the same molecular profile as in autologous CD4+ T cells. In addition, we established a humanized mouse model to investigate the in vivo interactions of EBV and HIV-1 upon coinfection. The respective mice that reconstitute human immune system components upon transplantation with CD34+ human hematopoietic progenitor cells could recapitulate aspects of EBV and HIV immunobiology observed in dual-infected patients. Upon coinfection of humanized mice, EBV/HIV dual-infected B cells could be detected, but were susceptible to CD8+ T-cell-mediated immune control.


Subject(s)
HIV Infections/immunology , HIV Infections/virology , Herpesvirus 4, Human/pathogenicity , Animals , B-Lymphocytes/metabolism , B-Lymphocytes/pathology , B-Lymphocytes/virology , CD4 Antigens/immunology , CD4 Antigens/metabolism , Coinfection , Disease Models, Animal , Disease Susceptibility/metabolism , Disease Susceptibility/virology , Epstein-Barr Virus Infections/immunology , HIV Infections/genetics , HIV Seropositivity , HIV-1/metabolism , HIV-1/pathogenicity , Hematopoietic Stem Cells/pathology , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/metabolism , Humans , Male , Mice , Mice, Inbred NOD , Receptors, CXCR4/metabolism , Receptors, CXCR4/physiology , T-Lymphocytes/immunology
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