Prions and Retroviruses

Question 1

what are Prions?

Answer 1

• conformational alteration of a normal CNS protein from a helix to a beta pleated sheet
• progressive degenerative CNS diseases are proteins without any nucleic acids at all
• formerly termed ‘slow viruses’ -but they are NOT VIRUSES

Question 2

how do you get prion viruses?

Answer 2

diseases inherited and others acquired (infectious)

Question 3

The basic mechanism of pathology?

Answer 3

proteins (MEANS THEYRE TOUGH) of abnormal conformation (prions) which act as templates for other body proteins (prion proteins) to adapt the abnormal conformations
= this causes proteins

Question 4

How are prions like proteins?

Answer 4

PRIONS are NOT ALIVE - therefore you cannot kill them
- being that prions are proteins - (they’re tough) and these agents are extremely resistant to all forms of inactivation except incineration

Question 5

PrPc vs PrPsc

Answer 5

PrPc - a normal surface component of neurons and glial cells (a helix) and is highly conserved between species
PrPsc - infectious form (beta pleated sheet) = prion
PrPsc - is very resistant to inactivation

Question 6

What do Prions cause?

Answer 6

1- Creutzfeld-Jacob Disease 
2- Scrapie (sheep and goats)
3- Kuru (spasticity and ataxia, kuru means to be afraid) KURU IS NOT EXTINCT
4- Fatal Familial Insomnia
5- Gerstmann-Straussler-Scheinker Syndrome (in humans and in animals - INHERITED)
6- Bovine Spongiform Encelopathy
7- Ungulate spongiform encephalopathy
8- Transmissible mink encephalopathy

Question 7

Creutsfeld-Jacob Disease

Answer 7

a progressive, fatal disease of the CNS - similar to Kuru - that is seen most frequently in teh 6th and 7th decades

Question 8

Initial signs of CJD?

Answer 8

changes in cerebral functions are thought to be initially psychiatric but are followed by dementia, spasticity, seizures and death after 1-5 years

Question 9

Variants?

Answer 9

• There is an inherited variant but the disease has been transmitted by human growth hormone and organ transplants, including corneas
• recently, a new variant in younger patients was described in britain which was ascribed to consumption of beef from cattle with mad cow disease

Question 10

Causes rules on beef consumption?

Answer 10

new rules on the food use of CNS tissues and the elimination of infected hers have brought variant CJD under control!

Question 11

Retroviruses

Answer 11

enveloped, ss RNA viruses taht encode reverse transcriptase (an RNA-dependent DNA polymerase) that copies the genome into dsDNA that can be integrated into the DNA of the host cell (provirus)s

Question 12

Two main groups of Retroviruses?

Answer 12

1 - Oncoviruses

2 - Lentiviruses - prototype lentivirus is visnavirus in sheep

Question 13

Oncoviruses

Answer 13

do not kill the viruses they infect, they just continue to produce virus particles infedinitely

Question 14

Oncoviruses transform the infected cells by what 3 mechanisms? (step one)

Answer 14

1 - encoding for an oncogene (not described in humans)

Question 15

Oncoviruses transform the infected cells by what 3 mechanisms? (step two)

Answer 15

2- insertional mutagenesis (disruption of growth regulator genes by the random insertion of the provirus (not known

Question 16

Oncoviruses transform the infected cells by what 3 mechanisms? (step three)

Answer 16

3- Activation of host cell growth regulator gene expression by viral protein

Question 17

Oncoviruses: HTVL 1 vs 2

Answer 17

HTVL 1 - associated with adult T-cell leukemia, a rare malignancy found in Japan, Africa and the Caribbean and with tropical spastic paraparesis
HTVL 2 - associated with hairy cell leukemia - Appear to be transmitted by sexual and arenteral routes, although the long incubation period (10-20 years) makes epidemiological investigation difficult.

Question 18

How was lentivirus discovered ?

Answer 18

In 1981 epidemiologists noted an increase in the number requests for pentamidine to treat PCP, Pneumoniae due to pneumocystis jerovecii (81 cases in children) a previously rare opportunistic pathogen
- cases then noted in San Fran and New York
Analysis showed that these cases were occurring mainly in young homosexual makes who had helper T cells and were susceptible to a number of infections

Question 18

Lentiviruses

Answer 18

the prototype virus of this type is visnavirus in sheep

Question 19

Why were young homosexual males an unusual profile?

Answer 19

It was usually cancer chemo patients or old people

Question 20

How was AIDS coined as what this was?

Answer 20

Almost all previously described immune deficiency diseases were conenital

Question 21

Who discovered AIDS?

Answer 21

The virus responsible was isolated first I’m France by Luc montagnier and then second by Robert Gallo in the US and was renamed HIV

Question 22

What did further analysis of HIV show?

Answer 22

That the virus is comparatively new and probably originated as a mutant simian virus in central
Africa

Question 23

Where were the first HIV cases found?

Answer 23

As early as 1939
In Germany (now Poland)

Question 24

What were AIDS cases related to?

Answer 24

- heterosexual activity, IV drug abuse, hemophilia, transfusion and vertical transmission NO EVIDENCE THAT CASUAL CONTACT CAN RESULT IN INFECTION

Question 25

HIV-1A

Answer 25

Mainly spreads heterosexually | -

Question 26

HIV 1B

Answer 26

- the predominant Strain in Europe and North America - spreads mainly via anal inter purse - soon after infection there is a flu-like illness which is associated with seroconversion

Question 27

what happens after 8-10 years?

Answer 27

There's a depletion in CD4 cells resulting in opportunistic infections and also dementia secondary to direct infection of the central nervous system

Question 28

When do you use the term AIDS?

Answer 28

When the advanced stage of the disease is reached - CD4 count < 200

Question 29

What about above 200??

Answer 29

Above 200 serology Positive for HIV antibiotics = you have HIV infections ***

Question 30

What is the count is over 500?

Answer 30

Immunity is normal

Question 31

Immunosuppressive is directly associated with what?

Answer 31

Immunosuppression correlates inversely to the CD4

Question 32

Risk to caregivers?

Answer 32

From a needle stick - approximately 1/300 (PEP can be given in these cases)

Question 33

How does HIV 2 spread?

Answer 33

Heterosexually

Question 34

What was aids originally called?

Answer 34

gay related immune deficiency

Question 35

Origins of HIV?

Answer 35

- SIVcpz found in Gabon serologically reacts with HIV-1 - entered human population through bush meat trade (Cameroon) - SIVcpz probably evolved into HIV-1 and HN-O - SIVsm 80-90% genetic homology with HIV-2 - HIV-1 = main cAuse of AIds in North America

Question 36

HIV -like viruses

Answer 36

- occur in cattle, lions, horses, sheep, goats and simians (SIV) - mostly benign but cause disease in equines and house cats - SIV first isolated from Japanese macaques - SIVgm (gm stands for African green monkey) , SIVcpz (chimpanzee) - SIVsm (sooty mangeby)

Question 37

Diagnosis of HIV

Answer 37

HAART - plus aggressive prophylaxis and treatment of opportunistic infections is not curative but the life span of those infected has improved markedly

Question 38

Biggest risk factor associated with new cases?

Answer 38

IV drug abuse

Question 39

Natural history of HIV

Answer 39

- complex interplay between viral replication and immunological defences - average time (without therapy) from infection to an AIDS-defining illness is ten years for HIV-1, longer for HIV-2 - there are nonprogressors, rapid progressives and HIV resistant people

Question 40

Degree of immunosuppression

Answer 40

CD4 counts of < 200 = AIDS | Drops less than 50 = DANGEROUS infection / viruses