Virus replication and interstitial pneumonia were studied in BALB/c mice inoculated intranasally with murine cytomegalovirus (MCMV). In normal mice MCMV replicated in lung tissue but did not produce any consistent histologic abnormalities through day 21. The addition of a single dose of cyclophosphamide (0.20 mg/g) 24 hr after virus inoculation resulted in a slight increase in lung virus titers on day 10. No histologic abnormalities were noted before day 10. However, 22 or 32 virus-infected mice treated with a single dose of cyclophosphamide but only two of 26 simultaneously mock-infected, cyclophosphamide-treated mice developed severe interstitial pneumonia 10-14 days after inoculation. In contrast, animals given cyclophosphamide (0.05 mg/g) every five days after the initial dose developed a 10-fold increase in lung virus titer, but interstitial pneumonia was not observed. These data suggest that the interstitial pneumonitis seen with MCMV pulmonary infection may be immunologically mediated rather than the result of direct viral damage to the lung.
HIV/AIDS is associated with reliable decrements in balance and peripheral sensory function which are variably sensitive to antiretroviral treatment. The implications of these findings for mobility, and workplace or operator safety, should be contemplated.
Calcium channel blockers reduce Ca++ flux through membrane channels and may inhibit intracellular Ca++-dependent synthetic and regulatory activities by binding to calmodulin. We have found that Verapamil, a calcium channel blocker, inhibits influenza virus replication in Madin-Darby canine kidney cells and in murine pulmonary macrophages and that this antiviral effect occurs with drug addition late in the replication cycle. Chlorpromazine, a drug which binds to calmodulin, also inhibited influenza virus replication in these tissue culture systems. We suggest that Verapamil and chlorpromazine inhibit influenza virus replication by interfering with calmodulin-dependent intracellular activities necessary for late synthetic steps or virus assembly steps and that calcium channel blockers provide a new probe for investigating influenza virus replication.
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