NUCLEIC-ACID BINDING-PROTEINS IN HIGHLY PURIFIED CREUTZFELDT-JAKOB-DISEASE PREPARATIONS

The nature of the infectious agent causing human Creutzfeldt-Jakob dis ease (CJD), a slowly progressive dementia, is controversial. As in scr apie, no agent-specific proteins or nucleic acids have been identified . However, biological features of exponential replication and agent st rain variation, as well as physical size and density data, are most co nsistent with a viral structure-i.e., a nucleic acid-protein complex. It is often assumed that nuclease treatment, which does not reduce inf ectious titer, leaves no nucleic acids of >50 bp. However, nucleic aci ds of 500-6000 bp can be extracted from highly purified infectious com plexes with a mass of almost-equal-to 1.5 x 10(7) daltons. It was ther efore germane to search for nucleic acid binding proteins that might p rotect an agent genome. We here use Northwestern blotting to show that there are low levels of nonhistone nucleic acid binding proteins in h ighly purified infectious 120S gradient fractions. Several nucleic aci d binding proteins were clearly host encoded, whereas others were appa rent only in CJD, but not in parallel preparations from uninfected bra in. Small amounts of residual host Gp34 (prion protein) did not bind a ny P-32-labeled nucleic acid probes. Most of the minor ''CJD-specific' ' proteins had an acidic pI, a characteristic of many viral core prote ins. Such proteins deserve further study, as they probably contribute to unique properties of resistance described for these agents. It rema ins to be seen ff any of these proteins are agent encoded.