PROTECTION AGAINST MURINE CYTOMEGALOVIRUS-INFECTION IN AGED MICE AND MICE WITH SEVERE COMBINED IMMUNODEFICIENCY DISEASE WITH THE BIOLOGICALRESPONSE MODIFIERS POLYRIBOSINIC-POLYCYTIDYLIC ACID STABILIZED WITH L-LYSINE AND CARBOXYMETHYLCELLULOSE, MALEIC-ANHYDRIDE DIVINYL ETHER ANDCOLONY-STIMULATING FACTOR-I

A variety of biological response modifiers (BRMs) have provided antivi ral protection to immunocompetent mice, and this prompted us to determ ine their efficacy against murine cytomegalovirus (MCMV) infection in immunocompromised mice-including the profoundly immunocompromised SCID mice and C57Bl/6 and B6D2F1 aged mice. SCID mice showed a marked decr ease (> 20-fold) in resistance to MCMV, while there was a slight decre ase (3-fold) in aged mice. In BRM antiviral protection studies, SCID m ice were almost completely protected against MCMV infection by the ple iotropic immunomodulators, MVE-2 and pICLC, but much less by the more selective CSF-1. pICLC-induced IFN and NK cell cytotoxicity were maint ained in SCID mice, suggesting that pleiotropic immunomodulatory effec ts may be required for antiviral protection in such a profoundly immun ocompromised model. pICLC also effectively protected aged mice against lethal MCMV infection and effectively induced IFN. These results emph asize the potential for BRM treatment in immunocompromised hosts.