Prion

Prion

Q. 1 Prion is a?
 A

DNA

 B

RNA

 C

Protein

 D

Polysacchride

Q. 1 Prion is a?
 A

DNA

 B

RNA

 C

Protein

 D

Polysacchride

Ans. C

Explanation:

Protein REF: Harrison’s 18th ed chapter 383

Prions are infectious proteins that cause degeneration of the central nervous system (CNS). Prion diseases are disorders of protein conformation, the most common of which in humans is called Creutzfeldt-Jakob disease

Disease

Host

Mechanism of Pathogenesis

Human

 

 

Kuru

Fore people

Infection through ritualistic cannibalism

iCJD

Humans

Infection from prion-contaminated hGH, duramater grafts, etc.

vCJD

Humans

Infection from bovine prion

fCJD

Humans

Germ-line mutations in PRNP

GSS

Humans

Germ-line mutations in PRNP

FFI

Humans

Germ-line mutation in PRNP (D178N, M129)

sCJD

Humans

Somatic mutation or spontaneous conversionof PrPC into PrPSc

sFI

Humans

Somatic mutation or spontaneous conversionof PrPC into PrPSc

CJD = Creutzfeldt-Jakob disease; FFI= fatal familial insomnia, GSS= Gerstmann-Straussler-Scheinker disease 


Q. 2

Regarding prion protein which of the following statment is true:

 A

It is protein product coded in viral DNA

 B

It catalyses abnormal folding of other proteins

 C

It protect disulfide bonds from oxidation

 D

It cleaves normal proteins

Q. 2

Regarding prion protein which of the following statment is true:

 A

It is protein product coded in viral DNA

 B

It catalyses abnormal folding of other proteins

 C

It protect disulfide bonds from oxidation

 D

It cleaves normal proteins

Ans. B

Explanation:

  • Prions propagate by transmitting a misfolded protein state
  • Alteration in the conformation of the protein
  • Normal α-helix structure is converted to β-sheet structure.
  • Acts as a template to guide the misfolding of more protein into prion form.
  • Aggregations of these abnormal  isoforms form highly structured amyloid fibers,
  • This altered structure is extremely stable, insoluble and accumulates in infected tissue
  • Causing tissue damage and cell death

Q. 3

All of the following diseases show abnormal folding of proteins except :

 A

Creutzfeldt-jabok disease

 B

Prion disease

 C

Multiple sclerosis

 D

Amylidosis

Q. 3

All of the following diseases show abnormal folding of proteins except :

 A

Creutzfeldt-jabok disease

 B

Prion disease

 C

Multiple sclerosis

 D

Amylidosis

Ans. C

Explanation:

Multiple sclerosis[Ref: Harrison 171h/e p. 2647; Harper 27th/e p. 38; Lippincott p. 20j

The process of protein folding is remarkably efficient, but sometimes it can go wrong.

Incorrectly folded proteins are considered to be the cause of many diseases.

Amvloidoses

  • The common characteristic of all amyloidoses is the collection of plaques of insoluble protein in the extracellular tissue which cannot be broken down by enzymes.
  • Their ordered structure gives them a crystal like properties and they are are made up of long filaments (fibrils) that are formed from densely packed p pleated sheets.
  • There are about 20 different proteins that can act as the building block of these fibrils each of which is associated with a different disease.
  • In the so called systemic amyloidoses, the precursors of these plaques are transported through the blood stream from their point of origin to the point of deposition.
  • Localized amyloidoses are of greater clinical significance as they mainly affect the central nervous system, the extracellular tissue of which is particularly susceptible to damage.

Alzheimer’s disease

  • One of the main characteristics of Alzhiemer’s disease is the accumulation of plaques of insoluble p amyloid in the brain.
  • The p amyloid plaques are formed by cleavage of amyloid precursor protein (APP) by two different enzymatic activities which release amyloid – p peptide fragments that are 40 or 42 amino acids long.
  • These then form fibrils which aggregate into insoluble clumps of p amyloid plaques that surround neurons and cause damage.
  • But this cleavage also occurs in healthy individuals and soluble p amyloid proteins are normal constituents of brain tissue.
  • How, then do the plaques form in Alzhiemer’s patients?
  • It is thought that the, mis folding of the protein, dramatically alters its properties.
  • In the normal protein, hydrophobic amino acids bury themsleves inside the protein right from the start of the folding.
  • However, if the protein folds wrongly, these hydrophobic amino acids are exposed and they rapidly seek out and bind to hydrophobic groups on other protein molecules forming the insoluble aggregates or plaques that are found in Alzhiemers patients.

Prion disease :

  • Prion are fatal neurodegenerative disease caused by transmissible proteins and are characterized by spongiform changes, astrocytic gliomas and neuronal loss from the deposition of insoluble protein aggregates in neural cells.
  • Prions are caused by human prion related protein (PrP) (a glycoprotein rich in a helix).
  • PrP is endogenous to the host and in most people, the PrP protein folds normally leaving the person healthy.
  • Rarely, a mutation in the PrP gene will allow the protein to be made incorrectly and it will fold incorrectly making a PrPsc prion. (Which is a glycoprotein rich in fi sheets).
  • These PrPsc prions when exposed to PrP, which is in the process of folding will encourage that PrP to fold incorrectly too, thus creating another PrPsc.
  • While PrP can be processed and cleaned out of a cell once it has been used, PrPsc is shaped differently enough so that it can’t be cleaned out and it aggregates inside the cell. These PrPsc aggregates quickly builds up into plaques destroying the nervous tissue.
  • Thus a pathological prion protein serves as the templates for the conformational transformation of normal PrP into PrPsc.
  • Creutzfeldt Jabok disease is caused by prions.

Other examples of disease caused by protein misfolding

  • Huntingtons
  • Parkinson’s
  • Amyotrophic lateral sclerosis

Q. 4

Secondary structure of prion proteins in prion disease like Creutz feldt-Jakob disease (CJD) is

 A

Beta sheets

 B

Beta bend

 C

Beta turus

 D

Alfa helix

Q. 4

Secondary structure of prion proteins in prion disease like Creutz feldt-Jakob disease (CJD) is

 A

Beta sheets

 B

Beta bend

 C

Beta turus

 D

Alfa helix

Ans. A

Explanation:

Beta sheets [Ref.. Harper 26/e, p 37,- Harrison 17/e, p 2646; Lippincott Biochem. 3/e, p 22]

  • Prions are caused by human prion related protein (PrP) (a glycoprotein rich in a helix).
  • PrP is endogenous to the host and in most people, the PrP protein folds normally leaving the person healthy.
  • Rarely, a mutation in the PrP gene will allow the protein to be made incorrectly and it will fold incorrectly making a PrPsc prion. (Which is a Rlycoprotein rich in ,beta sheets).

Remember

  • PrP                  –>           Made up of a helixo
  • PrPse               –> Made up of 13 shee 

Pathoeenesis of Prion’s disease

              

Normal endogenous human protein
(human prion related protein)

        (PrP)

         

It is a glycoprotein rich in
a helix and it folds
normally

     

Mutation in the
PrP protein

      

Folds improperly and result in PrPsc
protein (It is a glycoprotein
rich in (sheets)

         

PrPsc comes in contact
      with PrP

          

PrP too will fold uncorrectly
resulting in more PrPsc

         

Aggregation of
     PrPsc

        ↓

Destruction of nervous
      tissue

        ↓

Prion disease 


Q. 5 Prion includes
 A

DNA and RNA

 B

Only RNA

 C

Proteins

 D

Only DNA

Q. 5 Prion includes
 A

DNA and RNA

 B

Only RNA

 C

Proteins

 D

Only DNA

Ans. C

Explanation:

Proteins [Ref: Harrison 17th/e p. 2646, 2647; 1611i/e p. 2495]

  • Prions are infectious proteins that cause degeneration of the central nervous system.
  • They are infectious particles that lack nucleic acid.
  • Prions are composed largely, if not entirely of PrP molecules.

Four important points about prions are: ?

1)    Prions are the only known infectious pathogens that are devoid of nucliec acid, all other infectious agents possess genomes composed of either RNA or DNA that direct the synthesis fo their progeny.

2)    Prions disease may manifest as infectious, genetic and sporadic disorders; no other group of illness with a single etiology presents with such a wide spectrum of clinical manifestations.

3)    Prions disease results from the’accumulation of PrPsc the conformation of which differs substantially from that of its precursor PrP  PrPsc can exist in a variety of different conformations each of which seems to specify a particular disease phenotype.

Prions reproduce by binding to the normal cellular isoform of prim protein and stimulating conversion of PrP into the disease causing isoform.


Q. 6 Prions. True statement is:
 A Defect in protein folding
 B Cleave proteins
 C Scarpie is a human disease
 D Are non infectious
Q. 6 Prions. True statement is:
 A Defect in protein folding
 B Cleave proteins
 C Scarpie is a human disease
 D Are non infectious
Ans. A

Explanation:

Defect in protein folding


Q. 7

Which of the following is most resistant to antiseptics?

 A

Spore

 B

Prion

 C

Cyst

 D

Fungus

Q. 7

Which of the following is most resistant to antiseptics?

 A

Spore

 B

Prion

 C

Cyst

 D

Fungus

Ans. B

Explanation:

Prions are most resistant organisms to antiseptics. They are an infectious agent composed of a protein.

Ref: Antiseptics, Disinfection and Sterilization By McDonnell, 1st Edition, Page 33; Textbook of Microbiology By Ananthanarayan, 7th Edition, Pages 448, 567


Q. 8

Which of the following statements about Prions is true?

 A

They are infectious proteins

 B

They are made up of bacteria and virus

 C

They have rich nuclear material

 D

They can be cultured in cell free media

Q. 8

Which of the following statements about Prions is true?

 A

They are infectious proteins

 B

They are made up of bacteria and virus

 C

They have rich nuclear material

 D

They can be cultured in cell free media

Ans. A

Explanation:

Prions are infectious proteins devoid of any nucleic acid (DNA and RNA).

Ref: Medical Microbiology By Jawetz, 24th Edition, Page 581; Harrison’s Principles of Internal Medicine, 16th Edition, Page 2495; Textbook of Microbiology By Ananthanarayan, 7th Edition, Page 567


Q. 9

The secondary structure of prion particles is:

 A

Alfa helix

 B

Beta bends

 C

Beta sheets

 D

Beta turns

Q. 9

The secondary structure of prion particles is:

 A

Alfa helix

 B

Beta bends

 C

Beta sheets

 D

Beta turns

Ans. C

Explanation:

C i.e. Betasheets

There is no difference in amino acid & gene sequence, primary structure & post translational modifications between normal cellular isoform of non infectious (host) prion protein (PrPC) and infectious (pathological) prion proteins (PrPsc). The key to becoming infectious lies in 3 dimensional conformation i.e. a number of a -helices present in non infectious PrPC are replaced by /3 sheets in infectious (PrPse) formQ.


Q. 10

Choose the correct ones for the decreasing order of resistance to sterilization – 

 A

Prions, Bacterial spores, Bacteria

 B

Bacterial spore, Bacteria, Prions

 C

Bacteria,Prions, Bacterial spores

 D

Prions, Bacteria, Bacterial spores

Q. 10

Choose the correct ones for the decreasing order of resistance to sterilization – 

 A

Prions, Bacterial spores, Bacteria

 B

Bacterial spore, Bacteria, Prions

 C

Bacteria,Prions, Bacterial spores

 D

Prions, Bacteria, Bacterial spores

Ans. A

Explanation:

Ans. is ‘a’ i.e., Prions, Bacterial spores, Bacteria

.  Microorganisms differ in their susceptibility to different disinfecting agents.

  • Prions are resistant to almost all disinfectants except high doses of sodium hypochlorite.
  • Gram (+)ve bacteria are most susceptible to almost all disinfectants.

. Order of resistance to disinfectants:

Prion > spores> Hydrophilic virus > fungi > Acid fast arganisms (mycobacteria) > Gram (-) ye bacteria > Lipophilic virus > Gram (+)ve bacteria.

.  Hexachlorophene is very weak disinfectant. Almost all organisms are resistant to it.

. Sodium hypochlorite is best disinfectant, it is effective against all organisms including Prion.


Q. 11

Which of the following is most resistant to sterilization?

 A

Cysts

 B

Prions

 C

Spores

 D

Viruses

Q. 11

Which of the following is most resistant to sterilization?

 A

Cysts

 B

Prions

 C

Spores

 D

Viruses

Ans. B

Explanation:

Ans. is ‘b’ i.e., Prions


Q. 12

True about prion protein diseases is all, except ‑

 A

Myoclonus is seen in 10% of the patients

 B

Caused by infectious protein

 C

Brain biopsy is diagnostic

 D

Commonly manifests as dementia

Q. 12

True about prion protein diseases is all, except ‑

 A

Myoclonus is seen in 10% of the patients

 B

Caused by infectious protein

 C

Brain biopsy is diagnostic

 D

Commonly manifests as dementia

Ans. A

Explanation:

Ans. is ‘a’ i.e., Myoclonus is seen in 10% of patients


Q. 13

Prions are best killed by-

 A

Autoclaving at 121°C

 B

5% formaline

 C

Sodium hydroxide

 D

Sodium hypochloride

Q. 13

Prions are best killed by-

 A

Autoclaving at 121°C

 B

5% formaline

 C

Sodium hydroxide

 D

Sodium hypochloride

Ans. C

Explanation:

Ans. is ‘c’ i.e., Sodium hydroxide 

  • Incineration is apparently the only way of disinfecting prion-contaminated materials or tissues.
  • Boiling or irradiation have no effect and even routine autoclaving (at 121°C) is not reliable. Therefore, where there is a risk of exposure, surgeons use disposable instruments.
  • To sterilize reusable instruments, WHO currently recommends combined use of a strong solution of sodium hydroxide and extended autoclaving at 134°C.

“Autoclaving at 134°C for 5 hrs or treatment with 2 N NaOH for several hours is recommended for sterilization of prions”.


Q. 14

Which of following is correct about Prions ‑

 A

Long incubation period

 B

Destroyed by autoclaving at 121°C

 C

Nucleic acid present

 D

Immunogenic

Q. 14

Which of following is correct about Prions ‑

 A

Long incubation period

 B

Destroyed by autoclaving at 121°C

 C

Nucleic acid present

 D

Immunogenic

Ans. A

Explanation:

Ans. is ‘a’ i.e., Long incubation period 

  • There is long incubation period in prion disease.
  • Prions are not destroyed by autoclaving at 121°C.

“Autoclaving at 134°C for 5 hrs or treatment with 2 N NaOH for several hours is recommended for sterilization ofprions”.                                                  

  • Prions lack nucleic acid.
  • They are not immunogenic.

Q. 15

Creutzfeldt-Jacob disease is caused by – 

 A

Prion

 B

JC virus

 C

Genetic factors

 D

a and c

Q. 15

Creutzfeldt-Jacob disease is caused by – 

 A

Prion

 B

JC virus

 C

Genetic factors

 D

a and c

Ans. D

Explanation:

Ans. is ‘a’ i.e., Prion; ‘c’ Genetic factors 

.          CJD is a subacute presenile encephalopathy, with progressive incoordination and dementia, ending fatally in about a year.

.          Caused by Prion protein.

.          Disease occurs as both sporadic and inherited forms.

.          Most common human prion disease is sporadic CJD.

.          Iatrogenic CJD has occurred after corneal transplant and injection of pitutary growth hormone.

.          Clinical Manifestations

–         Deficits in higher cortical function

–         Dementia

–         90% patients exhibit myoclonus which persists during sleep in comparison of other involuntary movements.

–         Visual impairment, cerebellar gait, incoordination, pyramidal signs, extrapyramidal dysfunction, seizures.

.         Diagnosis

–        Only specific diagnostic test for CJD is measurement of Pr 13”’


Q. 16

Prions are –

 A

Made up of bacterial and viral particles

 B

Immunogenic

 C

infectious

 D

RNA particles

Q. 16

Prions are –

 A

Made up of bacterial and viral particles

 B

Immunogenic

 C

infectious

 D

RNA particles

Ans. C

Explanation:

Ans. is ‘c’ i.e., Infectious 

.   Prion is a small particle without any detectable nucleic acid (DNA or RNA), resistant to heat (90 degrees for 3 minutes); UV rays and nucleases. It is an infectious proteinaceous particle and sensitive to proteases.

.   Prions are not immunogenic –> immunosupression and interferon do not affect the course of the disease.

.   The lack of an inflammatory response in CJD and other prion diseases is an important pathologic feature of these degenerative disorders.


Q. 17

Regarding prion protein which of the following statment is true –

 A

It is protein product coded in viral DNA

 B

It catalyses abnormal folding of other proteins

 C

It protect disulfide bonds from oxidation

 D

It cleaves normal proteins

Q. 17

Regarding prion protein which of the following statment is true –

 A

It is protein product coded in viral DNA

 B

It catalyses abnormal folding of other proteins

 C

It protect disulfide bonds from oxidation

 D

It cleaves normal proteins

Ans. B

Explanation:

Ans. is ‘b’ i.e., It catalyses abnormal folding of other proteins

Prion

. Prions are infectious particle which contains protein only.

. They do not have nucleic acid.

Prions have been defined as ‑

Small proteinaceous infectious particle which resist inactivation by procedures that modify nucleic acids. How do the prions multiply in the absence of RNA or DNA ???.

.  Prions are proteins which are normally found in the body.

.  Proteins are basically long chain of amino acids.

.   The amino acid chains of the protein, fold, according to the instructions coded in the D.N.A.

Prions become infectious or pathogenic due to misfolding of the proteins.

.   Prions are normally present in human. The prim; protein, endogenous to the human is PrP (which is a glycoprotein rich in 13 sheets).

.  PrPsc is the infectious form of the Prion. (It is formed due to mutation in PrP)

.  There is’nt any primary structural or post translational modifications found between the normal and infectious form of the protein. The key to becoming infectious lies in changes in three dimensional conformation of PrP i.e. there is abnormality in protein folding (the a helical secondary structure of PrP changes to 13 sheet in PrPsc).

.   So, PrPsc is a misfolded PrP and this conformational difference cause PrPsc to resist proteolytic degradation.

.  Misfolded proteins are quite dangerous for the body because they possess a remarkable property that they can cause other normally folded prions to distort into the same misfolded state. Thus misfoldedproteins i.e. prions  are able to re licate and s read throu • hout tissue without usin • either DNA or RNA.

.   The infective agent is thus an altered version of a normal protein which acts as a template for converting more normal protein to the pathogenic conformation.



Q. 18

True about prions is –

 A

Encoded by viral genome

 B

 Associated with misfolding of protein 

 C

Non infectious

 D

Immunogenic

Q. 18

True about prions is –

 A

Encoded by viral genome

 B

 Associated with misfolding of protein 

 C

Non infectious

 D

Immunogenic

Ans. B

Explanation:

Ans. is ‘b’ i.e., Associated with misfolding of protein 

.   Prions become infectious or pathogenic due to misfolding of the proteins.

.   Prions are infectious proteinaceous particles and are not immunogenic.

.   Prions are normally present in mammals ( including human) and are encoded by the sequence of chromosome PrP gene of the mammals ( not by viral genome).


Q. 19

Fatal familial insomnia is associated with – 

 A

Prion disease

 B

Degeneration disease

 C

Neoplastic disease

 D

Vascular disease

Q. 19

Fatal familial insomnia is associated with – 

 A

Prion disease

 B

Degeneration disease

 C

Neoplastic disease

 D

Vascular disease

Ans. A

Explanation:

Ans. is ‘a’ i.e., Prion disease 


Q. 20

Which one of the following not a prion associated disease –

 A

Srapie

 B

Kuru

 C

Creutzfeldt-Jakob disease

 D

Alzheimer’s disease

Q. 20

Which one of the following not a prion associated disease –

 A

Srapie

 B

Kuru

 C

Creutzfeldt-Jakob disease

 D

Alzheimer’s disease

Ans. D

Explanation:

Ans. is ‘d’ i.e., Alzheimer’s disease


Q. 21

Which of the following is NOT a prion disease?

 A

Bovine spongiform encephalopathy

 B

Transmissible mink encephalopathy

 C

Scrapie

 D

Progressive multifocal leucoencephalopathy

Q. 21

Which of the following is NOT a prion disease?

 A

Bovine spongiform encephalopathy

 B

Transmissible mink encephalopathy

 C

Scrapie

 D

Progressive multifocal leucoencephalopathy

Ans. D

Explanation:

Ans. is ‘d’ i.e., Progressive multifocal leucoencephalopathy


Q. 22

Which one of the following is not a prion associated disease :

 A

Scrapie

 B

Kuru

 C

Creutzfeldt-Jakob disease

 D

Alzheimer’s disease

Q. 22

Which one of the following is not a prion associated disease :

 A

Scrapie

 B

Kuru

 C

Creutzfeldt-Jakob disease

 D

Alzheimer’s disease

Ans. D

Explanation:

Answer is D (Alzheimer’s disease):

Alzheimer’s disease is the most common cause of dementia in the Western World. It is not classified as a Prion disease.


Q. 23

Fatal familial insomnia is associated with :

 A

Prion disease

 B

Degenerative disease

 C

Neoplastic disease

 D

Vascular disease

Q. 23

Fatal familial insomnia is associated with :

 A

Prion disease

 B

Degenerative disease

 C

Neoplastic disease

 D

Vascular disease

Ans. A

Explanation:

Answer is A (Prion Disease):

Fatal familial insomnia is one of the commonly caused prion disease.

PRIONS refer to a class of proteinacious infectious particles without any detectable nucleic acid i.e. ‘virus like particles without the nucleic acid components’. – Ananthnarayan 6th /416

As can be expected they are sensitive to proteasesQ (contain protein) but resistant to nucleasese (do not contain nucleic acid) as well as to heat & UV rays.

The most commonly caused prion diseases include`:

  1. Kura
  2. Creutzfeildt – Jakob diseaseQ
  3. Gestermann – Straussler – Scheinker syndrome Q
  4. Fatal familial insomnia Q

Q. 24

Which of the following is not prion associated disease:     

March 2011

 A

Scrapie

 B

Kuru

 C

Creutzfeldt-jakob disease

 D

SSPE

Q. 24

Which of the following is not prion associated disease:     

March 2011

 A

Scrapie

 B

Kuru

 C

Creutzfeldt-jakob disease

 D

SSPE

Ans. D

Explanation:

  1. Scrapie
  2. latrogenic Creutzfeldt -Jakob disease ;

    Infection from prion contaminated human growth hormone, duramater graft, corneal transplant

  3. Kuru (human):Infection through ritualistic cannibalism
  4. Variant (CJD):Infection from bovine prion (Eating BSE infected beef)
  5. Familial CJD:Germline mutation in PRNP
  6. Sporadic CJD:Somatic mutation or spontaneous convention of PRPc into PRPsc
  7. Fatal familial insomnia:Germline mutation in PRNP
  8. Gestmann Strausster Scheinker:Germline mutation in PRNP
  9.  Bovine spongiform encephalopathy
  10. Transmissible mink encephalopathy

Q. 25

True about prions are all except:  

September 2009

 A

Associated with Cruetzfeldt-Jacob disease

 B

Heat labile

 C

Sensitive to proteases

 D

Infectious proteinaceous particles

Q. 25

True about prions are all except:  

September 2009

 A

Associated with Cruetzfeldt-Jacob disease

 B

Heat labile

 C

Sensitive to proteases

 D

Infectious proteinaceous particles

Ans. B

Explanation:

Ans. B: Heat labile

Prions are unconventional virus like agent.

Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein. They are resistant to heat (90 degree C for 3 minutes), UV rays and nucleases and sensitive to proteases. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). Bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans are among the most notable prion diseases.


Q. 26

Which prion disease affect human ‑

 A

Scrapie

 B

Madcow disease

 C

Kuru

 D

Bovine spongiform encephalopathy

Q. 26

Which prion disease affect human ‑

 A

Scrapie

 B

Madcow disease

 C

Kuru

 D

Bovine spongiform encephalopathy

Ans. C

Explanation:

Kuru prion Infection through ritualistic cannibalism



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