Mice transgenic for monocyte-tropic HIV type 1 produce infectious virus and display plasma viremia: A new in vivo system for studying the postintegration phase of HIV replication

To generate an in who system for in investigating the postintegration phase of HIV-1 replication, mouse lines transgenic for a full-length infectious proviral clone of a monocyte-tropic HIV-1 isolate, HIV-1(JR-CSF), were cons tructed. Leukocytes from two independent JR-CSF transgenic mouse lines prod uced HIV-1 that infected human PBMCs. Plasma viremia was detected in these mice at levels (mean, >60,000 HIV RNA copies/ml) comparable to those report ed for HIV-infected individuals. The levels of HN RNA in these mice increas ed several-fold after either treatment with the superantigen Staphylococcus enterotoxin B or infection with Mycobacterium tuberculosis. Thus, a provir us encoding a monocyte-tropic HIV-1 strain under the control of its LTR exp ressed as a transgene in mice can proceed through the postintegration repli cation phase and produce infectious virus. In addition, the presence of pla sma viremia that can be monitored by measuring plasma HIV-1 RNA levels perm its these mice to be used to study the impact of different interventions on modulating in vivo HIV-1 production. Therefore, these mice provide a novel manipulable system to investigate the in vivo regulation of HIV-1 producti on by factors that activate the immune system. Furthermore, this murine sys tem should be useful in delineating the role of human-specific factors in m odulating HIV-1 replication and investigating the irt vivo therapeutic effi cacy of agents that target the postintegration stages of HIV-1 replication.