orabase and Herpes-Simplex

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

An assay for the evaluation of antiviral and immunomodulator potency was developed using pure populations of cultured human monocytes. The assay involved culturing of human monocytes until they were fully susceptible (15-20 days) to lytic infection with HSV-1. When susceptible cells were cultured with recombinant interferon-alpha or a synthetic interferon inducer such as polyinosinic:polycytidylic acid prior to infection, a significant enhancement in resistance to the cytopathic effects of HSV-1 was observed. Likewise, a dose dependent reduction in cell lysis was observed when acyclovir was added immediately after virus infection. Monocyte resistance to HSV-1 was determined by the retention of pinocytic activity as determined by the uptake of neutral red dye. Relative pinocytic activity was quantitated using a simple colorimetric procedure. This antiviral assay can be completed in 48 h; is easy to perform, highly sensitive and reproducible.

Topics: Acyclovir; Adjuvants, Immunologic; Antigens, Viral; Antiviral Agents; Carboxymethylcellulose Sodium; Cytopathogenic Effect, Viral; Drug Evaluation; Herpes Simplex; Humans; In Vitro Techniques; Interferon Inducers; Interferon Type I; Monocytes; Poly I-C; Polylysine; Recombinant Proteins; Simplexvirus; Virus Replication

Infection of NMRI mice with increasing doses of six different strains of herpes simplex virus type 1 (HSV-1) induced increasing levels of neutralizing antibodies. In contrast, three strains of HSV-2, irrespective of the dose, induced only marginal antibody responses. Only strain HG 52 (HSV-2) at high doses of infection stimulated antibody formation. The virus content of some organs in 6- to 8-week-old mice appeared to be lower after HSV-2 than after HSV-1 infection. Application of immune-modulating drugs [silica or poly(I) X poly(C) coupled via L-lysine to CM-cellulose] resulted in little augmentation of antibody formation if compared to HSV-1 infection. Secondary infections with HSV-1 or HSV-2 after a primary dose of HSV-1 were followed by a marked booster response. In contrast, a primary infection with HSV-2 suppressed secondary responses of HSV-1 and HSV-2, thus indicating fundamental differences between the antibody-stimulating potency of HSV-1 and HSV-2 strains.

Topics: Animals; Antibodies, Viral; Ascitic Fluid; Carboxymethylcellulose Sodium; Cross Reactions; Cyclophosphamide; Female; Herpes Simplex; Immunologic Memory; Leucine; Mice; Mice, Inbred Strains; Neutralization Tests; Poly I-C; Polylysine; Rats; Rats, Inbred Strains; Serotyping; Silicon Dioxide; Simplexvirus; Species Specificity; Thymus Gland; Vaccines, Attenuated; Viral Vaccines

The efficacy of a herpes simplex virus type 1 (HSV-1) envelope antigen (EAG) preparation against HSV infection was studied in T cell competent and T cell deficient mice. Immuno-competent mice were successfully protected against herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infection when immunized 2 weeks prior to this infection with a heat-inactivated whole virus preparation or a HSV-1 envelope antigen (HSV-1 EAG) preparation. Since HSV-1 EAG was considerably less effective than the whole virus preparation, a poly.riboinosinic-poly.ribocytidylic acid complex with poly-L-lysine and carboxymethylcellulose (PICLC) was used as adjuvant. Immunization with HSV-1 EAG plus PICLC resulted in a pronounced increase of this protection rate as compared with that obtained after immunization solely with HSV-1 EAG. PICLC alone, however, offered no protection when given 2 weeks before challenge. In T cell deficient nu/nu mice no protection was achieved with HSV-1 EAG while their T cell competent, heterozygous littermates were protected. From these results it may be concluded that T cell competence is a prerequisite for establishing a protective immunity against HSV infection after immunization with HSV-1 EAG.

Topics: Adjuvants, Immunologic; Animals; Antigens, Viral; Carboxymethylcellulose Sodium; Herpes Simplex; Immunocompetence; Methylcellulose; Mice; Mice, Hairless; Mice, Inbred Strains; Mice, Nude; Peptides; Poly I-C; Polylysine; Simplexvirus; T-Lymphocytes; Viral Vaccines

An experimental model is described whereby human and monkey cervical tissues may be maintained as organ cultures for 21 and 40 days, respectively. Inclusion of sodium carboxymethyl cellulose in the culture medium prolongs the survival time of tissues considerably. The sequential cytologic changes associated with herpesvirus hominis type II (HVH-II) infection are reported. These changes are considered in relation to the possible causal role of HVH-II infection in cervical carcinogenesis.

Topics: Animals; Carboxymethylcellulose Sodium; Culture Media; Epithelium; Female; Haplorhini; Herpes Simplex; Humans; Models, Biological; Organ Culture Techniques; Precancerous Conditions; Uterine Cervical Neoplasms