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 K. P. Lam, Kwai Fung Hui, Simon Bredl, Erika Schlaepfer, Silvia Sorce, Andrea Zbinden, Riccarda Capaul, Jan D. Lünemann, Adriano Aguzzi, Aks Chiang, Werner Kempf, Alexandra Trkola, Karin J. Metzner, Markus G. Manz, Adam Grundhoff, Roberto F. Speck, Christian Münz
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.