Attenuated Creutzfeldt–Jakob Disease agents can hide more virulent infections

Abstract

We previously showed that a slow infectious strain of Creutzfeldt–Jakob Disease (CJD) can dramatically suppress the expression of a fast virulent agent injected intracerebrally 80 days later. While the slow SY agent eventually produced disease at ∼400 days, there was little evidence of the fast FU agent. However, two of 18 superinfected mice showed a minor increase in pathologic changes. To determine if FU was partially or completely suppressed, or if FU and SY agents formed a ‘chimera’ with intermediate incubation properties as predicted by prion theory, we passaged representative brains. All traces of FU were obliterated in typical brains of suppressed mice. The two aberrant mice however had mixed SY and FU infections, with FU reappearing at late stages of SY disease. Thus less virulent sporadic CJD infections in older people can conceal other agents such as variant CJD, the more recently evolved and virulent agent linked to bovine spongiform encephalopathy. This powerful model of agent-induced repression also implicates targets other than prion protein (PrP) in eliminating infection.