orabase and Cytomegalovirus-Infections

The role of interferon alpha/beta (IFN) induction by the immunomodulators pICLC and CL246,738 was investigated in CD-1 mice infected with murine cytomegalovirus (MCMV) or herpes simplex virus type 2 (HSV-2). Mice were treated with either normal sheep serum or anti-alpha/beta IFN antiserum, inoculated with the immunomodulators, and infected with virus. Because anti-IFN treatment also decreased natural resistance to HSV-2 and MCMV, two viral challenge doses were used to ensure that the mice with control serum or anti-IFN antiserum received biologically equivalent infections. Antiviral protection of pICLC and CL246,738 against HSV-2 infection was completely abrogated by treatment with anti-alpha/beta interferon antiserum. Mice treated with pICLC also lost antiviral protection against MCMV when interferon alpha/beta was depleted. These results indicate that induction of interferon alpha/beta appears to be a major mechanism for both natural resistance and pICLC-induced antiviral protection against MCMV and HSV-2 herpesvirus infections.

Topics: Acridines; Animals; Carboxymethylcellulose Sodium; Cytomegalovirus Infections; Female; Herpes Simplex; Herpesviridae Infections; Immunity, Innate; Immunologic Factors; Interferon Inducers; Interferon-alpha; Interferon-beta; Interferons; Mice; Mice, Inbred Strains; Poly I-C; Polylysine; Specific Pathogen-Free Organisms; Survival Analysis

A variety of biological response modifiers (BRMs) have provided antiviral protection to immunocompetent mice, and this prompted us to determine 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 decrease (> 20-fold) in resistance to MCMV, while there was a slight decrease (3-fold) in aged mice. In BRM antiviral protection studies, SCID mice were almost completely protected against MCMV infection by the pleiotropic immunomodulators, MVE-2 and pICLC, but much less by the more selective CSF-1. pICLC-induced IFN and NK cell cytotoxicity were maintained in SCID mice, suggesting that pleiotropic immunomodulatory effects may be required for antiviral protection in such a profoundly immunocompromised model. pICLC also effectively protected aged mice against lethal MCMV infection and effectively induced IFN. These results emphasize the potential for BRM treatment in immunocompromised hosts.

Topics: Animals; Carboxymethylcellulose Sodium; Cytomegalovirus Infections; Cytotoxicity, Immunologic; Immunity, Innate; Immunologic Factors; Interferons; Killer Cells, Natural; Macrophage Colony-Stimulating Factor; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, SCID; Poly I-C; Polylysine; Pyran Copolymer; Severe Combined Immunodeficiency