Nucleic acid binding proteins in highly purified Creutzfeldt-Jakob disease preparations.
The nature of the infectious agent causing human Creutzfeldt-Jakob disease (CJD), a slowly progressive dementia, is controversial. As in scrapie, no agent-specific proteins or nucleic acids have been identified. However, biological features of exponential replication and agent strain variation, as well as physical size and density data, are most consistent with a viral structure--i.e., a nucleic acid-protein complex. It is often assumed that nuclease treatment, which does not reduce infectious titer, leaves no nucleic acids of > 50 bp. However, nucleic acids of 500-6000 bp can be extracted from highly purified infectious complexes with a mass of approximately 1.5 x 10(7) daltons. It was therefore germane to search for nucleic acid binding proteins that might protect an agent genome. We here use Northwestern blotting to show that there are low levels of nonhistone nucleic acid binding proteins in highly purified infectious 120S gradient fractions. Several nucleic acid binding proteins were clearly host encoded, whereas others were apparent only in CJD, but not in parallel preparations from uninfected brain. Small amounts of residual host Gp34 (prion protein) did not bind any 32P-labeled nucleic acid probes. Most of the minor "CJD-specific" proteins had an acidic pI, a characteristic of many viral core proteins. Such proteins deserve further study, as they probably contribute to unique properties of resistance described for these agents. It remains to be seen if any of these proteins are agent encoded.
Sklaviadis
T
T
Yale Medical School, New Haven, CT 06510.
Akowitz
A
A
Manuelidis
E E
EE
Manuelidis
L
L
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002499:Centrifugation, Density Gradient; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D006224:Cricetinae; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D015180:Electrophoresis, Gel, Two-Dimensional; D015151:Immunoblotting; D008647:Mesocricetus; D008970:Molecular Weight; D016133:Polymerase Chain Reaction; D015347:RNA Probes; D016601:RNA-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism; D012016:Reference Values
D015342:DNA Probes; D004268:DNA-Binding Proteins; D015347:RNA Probes; D016601:RNA-Binding Proteins