HIV-1 replicating EBV-transformed B cells are efficiently immune controlled in vivo

HIV and EBV are human pathogens that cause a considerable burden to worldwide health. In combination these viruses are linked to AIDS-associated lymphomas. EBV, which transforms B cells, can make them susceptible to HIV-1 infection in a CXCR4 and CD4 dependent manner in vitro. We found that CXCR4-tropic HIV-1 integrates into the host genome with the same profile as in autologous CD4+ T cells. Additionally, we established a humanized mouse model to investigate the in vivo interactions of EBV and HIV-1 upon co-infection. 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, including failing immune control of EBV and enhanced EBV-driven tumorigenesis. Upon co-infection of humanized mice, EBV/HIV dual infected B cells could be detected, but seemed to be highly susceptible to CD8+ T cell mediated immune control.