Slow Viral or Prion Diseases

7/27/2019 Slow Viral or Prion Diseases

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Slow viral or prion diseases


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Introduction

Some chronic degenerative diseases of the central nervoussystem in humans are caused by "slow" or chronic, persistentinfections by classic viruses.

subacute sclerosing panencephalitis progressive multifocal leukoencephalopathy

Other diseases known as transmissible spongiformencephalopathies eg, Creutzfeldt-Jakob disease appear tobe caused by unconventional transmissible agents termed

"prions There may be incubation periods of years before clinical

manifestations of the infections become evident


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Slow Infections In Humans Viruses

SV40-like viruses (PML) measles virus (SSPE)

rubella virus Atypical Agents

Kuru Creutzfeld-Jakob disease (CJD) (new) variant CJD disease (vCJD=nvCJD )


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Progressive MultifocalLeukoencephalopathy

JC virus (JCV), a member of the family Polyomaviridae is theetiologic agent of progressive multifocal leukoencephalopathy

A central nervous system complication that occurs in someimmunosuppressed individuals

Now seen in a significant proportion (about 5%) of patientswith AIDS; however, as ART slows pogression of HIVinfections, fewer patients develop this disease.

Demyelination in the central nervous system of patients withprogressive multifocal leukoencephalopathy results fromoligodendrocyte infection by polyomaviruses.


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SYMPTOMS

weakness speech problems cognitive problems headaches visual problems sensory loss seizures

http://library.med.utah.edu/WebPath/TUTORIAL/AIDS/AIDS076.html


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Subacute Sclerosing Panencephalitis

A rare disease of young adults caused by measles virus, with slowlyprogressive demyelination in the central nervous system ending indeath

Large numbers of viral nucleocapsid structures are produced inneurons and glial cells.

There is restricted expression of the viral genes that encodeenvelope proteins, so the virus persistently infecting neural cellslacks proteins needed for the production of infectious particles.

Patients with subacute sclerosing panencephalitis have high titersof antimeasles antibody

Reduced efficiency of measles virus transcription in differentiatedbrain cells is important in maintaining the persistent infection thatleads to subacute sclerosing panencephalitis


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Transmissible SpongiformEncephalopathy (TSEs)

The Mad Cow Disease in Cows, Scrapie in Sheep, theCreutzfeldt-Jakob Disease in human beings belong to aclass of disease called Transmissible SpongiformEncephalopathy (TSEs)

Initially thought to be due to slow viruses, due to thelong incubation period between time of infection andappearance of disease, these are now known to be

caused by agents called prions


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Transmissible Spongiform Encephalopathy (TSE) WhatAre They?

Transmissible Spongiform Encephalopathy (TSEs) are rareforms of progressive neurodegenerative disorders that affectboth humans & animals

They are caused by similar agents (prions)

They are called so because they produce spongiform changesin the brain

Also, the agent causing the disease is found at the highest titrein the brain


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Transmissible SpongiformEncephalopathies (Prion Diseases)

Degenerative central nervous system diseaseshave similar pathologic features

kuru

Creutzfeldt-Jakob disease Gerstmann-Strussler-Scheinker syndrome Fatal familial insomnia of humans Scrapie of sheep Transmissible encephalopathy of mink Bovine spongiform encephalopathy of cattle Chronic wasting disease of deer


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Transmissible SpongiformEncephalopathies (Prion Diseases)

These diseases are described as transmissiblespongiform encephalopathies. The causativeagents are not conventional viruses;

Infectivity is associated with proteinaceousmaterial devoid of detectable amounts of nucleicacid. The term "prion" is used to designate thisnovel class of agents.

Although the etiologic agent may be recoverablefrom other organs, the diseases are confined tothe nervous system.


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Symptoms Neurodegeneration and spongiform changes Amyloid plaques may be present. Long incubation periods (months to decades) precede the

onset of clinical illness and are followed by chronic

progressive disease (weeks to years). The diseases are always fatal, with no known cases of

remission or recovery. The host shows no inflammatory response and no immune

response (the agents do not appear to be antigenic); No production of interferon is elicited; No effect on host B cell or T cell function


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Symptoms

Immunosuppression of the host has no effecton pathogenesis

chronic inflammation induced by other factors(viruses, bacteria, autoimmunity) may affectprion pathogenesis

prions accumulate in organs with chroniclymphocytic inflammation


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Scrapie A protease-resistant protein Can be purified from scrapie-infected brain and is

designated prion protein PrP.

Preparations containing only PrP and no detectablenucleic acid The level of PrP Sc is increased in infected brains

because the protein becomes resistant to degradation.

Genetic susceptibility to scrapie infection is associatedwith point mutations in the PrP C gene, and micegenetically altered to be devoid of PrP C are resistant toscrapie.


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Mad Cow Disease (BSE) Scientific Name: Bovine Spongiform Encepalopathy

It is found on any type of cloven hoofed animalssuch as: pigs, sheep, and cattle

Sheep: Scrapie Spongiform Encepalopathy. There is a human form called Creutzfeldt-Jakobs

Disease


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Bovine Spongiform Encephalopathy andNew Variant Creutzfeldt-Jakob Disease

A disease similar to scrapie, designated bovine spongiformencephalopathy (BSE), or "mad cow disease," emerged in cattle inGreat Britain in 1986.

This outbreak was traced to the use of cattle feed that containedcontaminated bone meal from scrapie-infected sheep and BSE-

infected cattle carcasses. In 1996, a new variant form of Creutzfeldt-Jakob disease (CJD) was

recognized in the United Kingdom that occurred in younger peopleand had distinctive pathologic characteristics similar to those of BSE.

It is now accepted that the new variant forms of CJD and BSE arecaused by a common agent, indicating that the BSE agent hadinfected humans.

Through 2004, 150 people had been diagnosed with new variantCJD in England, and most had died.


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Bovine SpongiformEncephalopathy (BSE) is so

named because of thespongy appearance of thebrain tissue of infectedcattle (and also in thehuman beings) whenexamined under amicroscope


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Kuru and Classic Creutzfeldt-JakobDisease

Two human spongiform encephalopathies arekuru and the classic form of CJD.

Brain homogenates from patients have

transmitted both diseases to nonhumanprimates. Kuru occurred only in the eastern highlands of

New Guinea and was spread by customssurrounding ritual cannibalism of dead relatives.

Since the practice has ceased, the disease hasdisappeared.


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Bovine Spongiform Encephalopathy (BSE) was first

described in the UK in 1985 as a prion-based diseasethat affected cattle.

In 1996 it was first detected in a human being

It was suspected at that time (which turned out to becorrect) that humans were contracting the diseasefrom eating cows that had been infected with BSE

In humans, it has been named the Creutzfeldt-JakobDisease (CJD)

Origins of CJD


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CJD is classified into 2 forms: Classic CJD & Variant CJD

Classic CJD can be transmitted to other species, however otheranimals cannot carry it.

Sub classified into: Sporadic CJD and Iatrogenic CJD

Sporadic CJD - >85% of Classic CJD cases

Most common between 50 75 years

Characterized by rapidly increasing dementia

Iatrogenic CJD - < 5% Classic CJD cases

Transmission of prion via medications & surgical equipment

Types of CJD


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vCJD Variant Creutzfeldtt-Jakob Disease

(vCJD), is caused by theconsumption of BSE infected meatproducts

The first 10 cases of variant CJDwere observed in 1996, ten yearsafter the outbreak of BSE in the UK

Variant CJD seems to affect mostly

young patients


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CJD causes fatal degradation of brain tissue & the nervous system

The symptoms include loss of expressiveness, muscular tremble,spasm, impaired muscle coordination, loss of memory &dementia

vCJD patients also display unusual psychiatric problems

There is no cure for CJD

The condition of the patient deteriorates, finally resulting indeath

Clinical Symptoms


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At Present, there is no Cure for the Mad CowDisease(Bovine Spongiform Encephalitis) and for the

Creutzfeldt-Jakob Disease

Prevention is the only availableoption


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CJD in humans develops gradually, withprogressive

dementia ataxia myoclonus

leads to death in 5 12 months


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Two familial forms of CJD are Gerstmann-Strussler-Scheinker syndrome and Fatal familial insomnia.

These diseases are rare (10 15% of CJD cases)and are due to inheritance of mutations in thePrP gene.


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Iatrogenic CJD has been transmitted accidentally by contaminated growth hormone preparations from human cadaver

pituitary glands by corneal transplant by contaminated surgical instruments cadaveric human dura mater grafts used for surgical repair of head

injury. It appears that recipients of contaminated dura mater grafts remain at

risk of developing CJD for at least 16 years following receipt of grafts. There is currently no suggestion of CJD transmission by blood or blood

products, although the potential is there. A protein very similar to scrapie PrP Sc is present in brain tissue infected

with classic CJD. It has been speculated that the agent of CJD wasderived originally from scrapie-infected sheep and transmitted tohumans by ingestion of poorly cooked sheep brains

Documents

Slow Viral or Prion Diseases