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

在人源化小鼠中,EBV使B细胞易受HIV-1感染。

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作者: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 Bredl ,Erika 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

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.

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