Evidence from animal and human studies has suggested an increase in antigen-specific IgE production during viral infections and elevated levels of IgE are characteristic of human asthma and allergy. Here, we provide molecular evidence for the role of viral infection and activation of the anti viral protein kinase (PKR, dsRNA-activated protein kinase) in the induction of IgE class switching and expression of IL-4 and IL-13. The presence of dsRNA, a known component of viral infection and an activator of PKR, induced IgE class switching as detected by the expression of germline ε in the human Ramos B cell line. Furthermore, dsRNA treatment of Ramos cells resulted in the activation of PKR and in vivo activation of NFκB complex. Interestingly, infection of Ramos cells with Rhinovirus (common cold virus), serotypes 14 and 16, resulted in the induction of germline ε. To further evaluate the role of PKR in the viral induction of IgE class switching, we infected Ramos cells with two different vaccinia virus (cowpox virus) strains. Infection with wild type vaccinia virus failed to induce germline ε, however, a deletion mutant of vaccinia virus (VP1080) lacking the PKR inhibitory polypeptide E3L, induced the expression of germline ε. DsRNA treatment of Ramos cells also resulted in a dose-dependent increase in IL-4 and IL-13 mRNA. Collectively, the results define a common mechanism for viral infections in Th2 responses and subsequent induction of IgE-mediated disorders such as allergy and asthma.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology