The effect of oral chloramphenicol (CHPC) on the development of immune responses to canine distemper virus (CDV) in Beagle pups was studied. Dogs were treated with CHPC for 14 days at a dose of 50 mg/kg, three times a day. Hematologic changes in CHPC-treated dogs included: polychromasia, anisocytosis, and target cell formation of red blood cells concurrent with vacuolation of lymphocytes and basophilic granule formation in neutrophils. Dogs given this therapy showed normal in vivo and in vitro immune responses after CDV vaccination and survived a virulent CDV challenge, whereas untreated, unvaccinated dogs became ill or died after challenge exposure. The results of this study indicate that CHPC therapy does not interfere with either the prechallenge immune response to attenuated viral antigen or the efficient immune mechanisms invoked during virulent virus challenge.

To generate an in vivo system for 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-1JR-CSF, were constructed. Leukocytes from two independent JR-CSF transgenic mouse lines produced 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 reported for HIV-1-infected individuals. The levels of HIV RNA in these mice increased several-fold after either treatment with the superantigen Staphylococcus enterotoxin B or infection with Mycobacterium tuberculosis. Thus, a provirus encoding a monocyte-tropic HIV-1 strain under the control of its LTR expressed as a transgene in mice can proceed through the postintegration replication phase and produce infectious virus. In addition, the presence of plasma viremia that can be monitored by measuring plasma HIV-1 RNA levels permits 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 production by factors that activate the immune system. Furthermore, this murine system should be useful in delineating the role of human-specific factors in modulating HIV-1 replication and investigating the in vivo therapeutic efficacy of agents that target the postintegration stages of HIV-1 replication.