MxA gene expression after live virus vaccination: a sensitive marker for endogenous type I interferon.

Abstract

MxA gene expression is known to be regulated tightly and exclusively by type I interferons (IFNs). The kinetics of MxA gene expression was analyzed in peripheral blood mononuclear cells from 11 healthy volunteers vaccinated with the 17-D strain of yellow fever virus. A reliable induction of MxA RNA and MxA protein was found in the absence of easily detectable serum IFN activity. Thus, steady-state MxA RNA levels were elevated 8- to 30-fold above prevaccination levels on day 5 after vaccination. The average increase of MxA protein was approximately 50-fold. In contrast, no induction of MxA RNA or MxA protein was detectable in 3 similarly vaccinated controls who were immune because of previous vaccinations. The IFN marker 2'-5'-oligoadenylate (2-5A) synthetase known to react to both type I and type II IFNs showed a similar response but did not differentiate equally well between nonimmune and immune vaccinees. beta 2-microglobulin and neopterin reacted poorly, remaining at low levels within the normal range. These results demonstrate that MxA gene expression is a good marker for detecting minute quantities of biologically active type I IFN during viral infections.