Biological response modifier-mediated resistance to herpesvirus infections requires induction of alpha/beta interferon.
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.
Kunder
S C
SC
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
Kelly
K M
KM
Morahan
P S
PS
D000166:Acridines / Q000494:pharmacology; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology / Q000031:analogs & derivatives; D003586:Cytomegalovirus Infections / Q000276:immunology; D005260:Female; D006561:Herpes Simplex / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology*; D007369:Interferon Inducers / Q000494:pharmacology; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D007372:Interferons / Q000096:biosynthesis*; D051379:Mice; D008815:Mice, Inbred Strains; D011070:Poly I-C / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology / Q000031:analogs & derivatives; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis
D000166:Acridines; D007155:Immunologic Factors; D007369:Interferon Inducers; D016898:Interferon-alpha; D011107:Polylysine; D016899:Interferon-beta; C019531:poly ICLC; C045570:3,6-bis(2-piperidinoethoxy)acridine trihydrochloride; D007372:Interferons; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C