For example, antiretroviral drugs as either preexposure prophylaxis or treatment Selleckchem Erlotinib of established infection have been examined

in mice with reconstituted human immune system components, and preexposure prophylaxis with these reagents has been shown to block rectal transmission [26, 32-34]. In addition, experimental therapies against HIV infection using either antiviral siRNA delivery to T cells, siRNA-mediated silencing of the CCR5 coreceptor and of viral proteins, or cyclin-dependent kinase blockade to inhibit viral replication have been successfully employed in these mouse models [35-37]. Thus mice with reconstituted human immune system components recapitulate HIV infection and can be used as a preclinical model for therapies against this viral infection. Besides HIV, infection with the human tumor virus EBV has been studied in this in vivo model of the human immune system [6, 38-40]. For these studies the viral strain B95–8 see more was used almost exclusively, which was originally isolated from a patient with symptomatic primary EBV infection, called infectious mononucleosis [41]. i.p. infection with increasing infectious doses of EBV leads to

asymptomatic persistent infection, lymphoproliferative disease, or even hemophagocytic lymphohistiocytosis [40, 42]. During persistent infection, B cells primarily harbor the virus and strong evidence exists for both latent EBV infection as well as a low level of lytic EBV replication [38]. These persistently infected B cells can be purified from EBV-carrying animals and cultured in vitro as immortalized lymphoblastoid cell lines. They express all eight latent EBV antigens in so-called latency type III. However, it is much less clear if other for EBV latencies also develop in mice with reconstituted human immune system components, such as latency 0, which is found without

any EBV protein expression in memory B cells of healthy virus carriers; latency I, which is found in Burkitt’s lymphoma and homeostatic proliferating memory B cells in humans; and latency II, which is present in Hodgkin’s lymphoma and germinal center B cells in healthy EBV carriers [43]. Immunohistochemical studies provide some evidence to support the development of latencies 0, I, and II in reconstituted mice [44, 45]. However, false-negative immunohistochemistry for EBV gene products might erroneously suggest the presence of latency types other than latency III. Interestingly, EBV-encoded miRNAs are required to establish systemic persistent infection [46]. Furthermore, a latent nuclear antigen of the virus, called Epstein-Barr nuclear antigen 3B (EBNA3B), suppresses tumor formation in vivo [47].