ACTIVATION OF ANTIVIRAL PROTEIN-KINASE LEADS TO IMMUNOGLOBULIN-E CLASS SWITCHING IN HUMAN B-CELLS

An epidemiologic association between viral infections and the onset of asthma and allergy has been documented. Also, evidence from animal an d human studies has suggested an increase in antigen-specific immunogl obulin E (IgE) production during viral infections, and elevated levels of IgE are characteristic of human asthma and allergy. Here, we provi de molecular evidence for the roles of viral infection and of activati on of the antiviral protein kinase (PKR) (double-stranded-RNA [dsRNA]- activated protein kinase) in the induction of IgE class snitching, The presence of dsRNA, a known component of viral infection and an activa tor of PKR, induced IgE class switching as detected by the expression of germ line E in the human Ramos B-cell line. Furthermore, dsRNA trea tment of Ramos cells resulted in the activation of PKR and in vivo act ivation of the RIF-KB complex. Interestingly, infection of Ramos cells with rhinovirus (common cold virus) serotypes 14 and 16 resulted in t he induction of germ line E expression 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. Infect ion with wild-type vaccinia virus failed to induce germ line E express ion; however, a deletion mutant of vaccinia virus (VP108O) lacking the PKR-inhibitory polypeptide E3L induced the expression of germ line ep silon. Collectively, the results of our study define a common molecula r mechanism underlying the role of viral infections in IgE class switc hing and subsequent induction of IgE-mediated disorders such as allerg y and asthma.