MECHANISM OF VIRUS-INDUCED IG SUBCLASS SHIFTS

Infection of mice with live viruses leads to a dramatic increase in th e amount of IgG2a Ig with a consequent shift in the ratio of IgG1/IgG2 a. To examine the Ig subclass shift induced by viral infection, we cha llenged mice with live virus, inactivated virus, or replication-defect ive mutant viruses that were able to infect cells and produce some vir al proteins but were not able to complete a replicative cycle. While k illed (or inactivated) virus was capable of inducing HSV-specific anti body, it did not stimulate a shift in the subclass of the total Ig. Re plication-defective mutant viruses that fail to express a functional I CP8 or ICP27 protein, but not a mutant expressing a defective ICP4 pro tein, were able to stimulate the shift. Thus, only a portion of the ly tic cycle is sufficient to induce the shift. At least part of the effe ct is mediated by IFN-gamma.