The Role of Interferons in Rotavirus Infections and Protection
| Autor: | Monica M. McNeal, Richard L. Ward, John L. VanCott, Anthony H.-C. Choi |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Diarrhea
Rotavirus Time Factors Recombinant Fusion Proteins viruses Immunology Administration Oral Enzyme-Linked Immunosorbent Assay Virus Replication medicine.disease_cause Rotavirus Infections Interferon-gamma Mice Antigen Virology medicine Animals Interferon gamma STAT1 Viral shedding Antigens Viral Administration Intranasal Mice Knockout Mice Inbred BALB C biology Viral Vaccine virus diseases Viral Vaccines Cell Biology Mice Inbred C57BL Viral replication Interferon Type I biology.protein Capsid Proteins medicine.symptom medicine.drug |
| Zdroj: | Journal of Interferon & Cytokine Research. 23:163-170 |
| ISSN: | 1557-7465 1079-9907 |
| DOI: | 10.1089/107999003321532501 |
| Popis: | Type I and type II interferons (IFNs) play a critical role in control of a number of viral infections. To study whether altered and reduced functional capacities of type I and type II IFNs would affect rotavirus-induced diarrhea and viral replication, we obtained signal transducers and activators of transcription 1 (Stat1) knock-out mice (Stat1(-/-)) that lack many IFN-induced responses. We found that suckling Stat1(-/-) and immunocompetent mice orally infected with rotavirus experienced diarrhea and shed rotavirus with similar intensity. However, adult Stat1(-/-) mice shed up to 100-fold more homologous murine rotavirus and heterologous rhesus rotavirus antigen in their stools than did immunocompetent mice 2-6 days after infection. Clearance of rotavirus in stools from adult Stat1(-/-) mice occurred at the same time as in wild-type (WT) control mice. Clearance in Stat1(-/-) mice correlated with a potent antibody response and a mixed Th1 and Th2 response, whereas in WT control mice, clearance correlated with a weaker antibody response and a polarized Th1 response. Stat1(-/-) mice were fully protected against subsequent challenge. Moreover, vaccination of adult Stat1(-/-) mice with a rotavirus VP6 protein and the mucosal adjuvant Escherichia coli heat-labile toxin LT (R192G) elicited 94% protection, as measured by the total reduction in viral shedding for the group in comparison to unimmunized controls. Thus, modulating IFN function through the loss of Stat1 caused a defective innate immune response in adult mice but had no effect on rotavirus-induced diarrhea and replication in suckling mice. Furthermore, adult Stat1(-/-), IFN-gamma, and IFN-alpha/beta receptor(-/-) (IFNAR-2(-/-)) mice infected with rotavirus or vaccinated with VP6 vaccine and adjuvant were fully protected against rotavirus shedding following a subsequent challenge with rotavirus. |
| Databáze: | OpenAIRE |
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