EBV renders B cells susceptible to HIV-1 in humanized mice

Donal McHugh, Renier Myburgh, Nicole Caduff, Michael Spohn, Yik Lim Kok, Christian W. Keller, Anita Murer, Bithi Chatterjee, Julia Rühl, Christine Engelmann, Obinna Chijioke, Isaak Quast, Mohaned Shilaih, Victoria P. Strouvelle, Kathrin Neumann, Thomas Menter, Stephan Dirnhofer, Janice Kp Lam, Kwai F. Hui, Simon BredlErika Schlaepfer, Silvia Sorce, Andrea Zbinden, Riccarda Capaul, Jan D. Lünemann, Adriano Aguzzi, Alan Ks Chiang, Werner Kempf, Alexandra Trkola, Karin J. Metzner, Markus G. Manz, Adam Grundhoff, Roberto F. Speck, Christian Münz

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2 Citations (Scopus)

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.

Original languageEnglish
Article numbere202000640
Number of pages19
JournalLife Science Alliance
Volume3
Issue number8
DOIs
Publication statusPublished - 1 Aug 2020

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