SN7 SHORT NOTE 5M

Describe prions and the slow virus infections.

Microbiology · 2nd Professional — Para-Clinical

Prions

A prion is an infectious agent consisting of protein alone, with NO nucleic acid — an abnormally folded form of a normal host protein that induces the normal form to misfold. The term is a contraction of "proteinaceous infectious particle" (Prusiner).

The normal cellular protein PrPC is a host-coded glycoprotein, rich in alpha-helix, present on neurons → The abnormal PrPSc (scrapie form) has the same amino acid sequence but is folded predominantly into beta-pleated sheet → PrPSc acts as a template, converting normal PrPC into the abnormal form — an autocatalytic process → The abnormal protein is resistant to proteases and accumulates → It aggregates into amyloid plaques; neurons die → spongiform change — vacuolation of grey matter — with gliosis and NO inflammatory response → Progressive fatal neurodegeneration after an incubation of years to decades

Extraordinary resistance — prions withstand standard autoclaving, formaldehyde, alcohol, boiling, UV and ionising radiation, all of which act on nucleic acid or on ordinary proteins. Inactivation requires 134°C for 18 minutes, 1N sodium hydroxide, or sodium hypochlorite, and disposable instruments or incineration are preferred
They provoke NO immune or inflammatory response — no antibody, no fever, no cellular infiltrate — because the protein is a self protein. There is therefore no serological test

Disease	Host and mode	Features
Creutzfeldt-JAKOB disease (sporadic)	85% of human cases; no identified source	Rapidly progressive dementia with myoclonus and ataxia in the elderly; characteristic periodic sharp waves on the EEG; death within a year
Iatrogenic CJD	Transmitted by medical procedures	Corneal and dura mater grafts, cadaveric growth hormone and gonadotrophin, and contaminated neurosurgical instruments — which is why prion resistance to sterilisation matters clinically
Variant CJD	From eating beef from cattle with bovine spongiform encephalopathy ("mad cow disease")	Affects younger people, with early psychiatric and sensory symptoms; the "pulvinar sign" on MRI; a longer course
Familial CJD, GSS, fatal familial insomnia	Inherited PRNP gene mutations	Autosomal dominant
Kuru	Ritual cannibalism among the Fore people of Papua New Guinea	Cerebellar ataxia and tremor; disappeared after the practice ceased — the illness that first demonstrated transmissibility

CLINICAL PEARL

A prion transmits information without carrying any genetic material, which was thought impossible. The "protein only" hypothesis contradicted the assumption that heritable information must reside in nucleic acid, and was resisted for years before Prusiner received the Nobel Prize for it. The practical consequences follow directly: no nucleic acid means no antibiotic target, no serology, and resistance to every sterilising method aimed at DNA.

Slow Virus Infections

Disease	Agent	Features
Subacute sclerosing panencephalitis (SSPE)	Defective measles virus persisting in the brain	Occurs 5 to 15 years after measles, particularly when the infection was before the age of 2. Progressive intellectual decline, myoclonic jerks, seizures and death. Very high measles antibody titres in CSF; periodic complexes on EEG. Prevented entirely BY measles vaccination
Progressive multifocal leukoencephalopathy (PML)	JC polyomavirus	Reactivation in profound immunosuppression — AIDS, and with natalizumab and rituximab; multifocal demyelination with focal deficits; treatment is restoration of immunity
Progressive rubella panencephalitis	Rubella virus	Rare, after congenital rubella
HIV encephalopathy	HIV	Direct CNS infection causing dementia

"Slow virus" infections differ fundamentally from prion disease — they are caused by conventional viruses with nucleic acid that persist and cause disease after a very long incubation, and they do provoke an immune response, which is how they are diagnosed

Applied Aspects

Measles vaccination prevents SSPE, and this is among the strongest arguments for immunisation; SSPE still occurs in India where coverage has been incomplete, and it is invariably fatal
Vaccinate against measles on time; infection before the age of 2 carries the highest risk of SSPE, so delay is not neutral
Use disposable instruments or dedicated instrument sets in suspected prion disease, and never return them to the general pool; standard autoclaving does not decontaminate them
Iatrogenic CJD is a reminder that human-derived biological products carry risk; cadaveric growth hormone and dura mater grafts have been replaced by recombinant and synthetic alternatives for this reason
Consider PML in an immunosuppressed patient with progressive focal neurological deficits, and remember that it is a recognised complication of natalizumab and rituximab, which changes the risk-benefit discussion before those drugs are started
There is no treatment for any prion disease, and management is supportive; prevention through surgical practice, tissue sourcing and food safety is the only effective intervention

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