Prions and Retroviruses Flashcards
what are Prions?
- 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
how do you get prion viruses?
diseases inherited and others acquired (infectious)
The basic mechanism of pathology?
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
How are prions like proteins?
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
PrPc vs PrPsc
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
What do Prions cause?
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
Creutsfeld-Jacob Disease
a progressive, fatal disease of the CNS - similar to Kuru - that is seen most frequently in teh 6th and 7th decades
Initial signs of CJD?
changes in cerebral functions are thought to be initially psychiatric but are followed by dementia, spasticity, seizures and death after 1-5 years
Variants?
- 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
Causes rules on beef consumption?
new rules on the food use of CNS tissues and the elimination of infected hers have brought variant CJD under control!
Retroviruses
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
Two main groups of Retroviruses?
1 - Oncoviruses
2 - Lentiviruses - prototype lentivirus is visnavirus in sheep
Oncoviruses
do not kill the viruses they infect, they just continue to produce virus particles infedinitely
Oncoviruses transform the infected cells by what 3 mechanisms? (step one)
1 - encoding for an oncogene (not described in humans)
Oncoviruses transform the infected cells by what 3 mechanisms? (step two)
2- insertional mutagenesis (disruption of growth regulator genes by the random insertion of the provirus (not known
Oncoviruses transform the infected cells by what 3 mechanisms? (step three)
3- Activation of host cell growth regulator gene expression by viral protein
Oncoviruses: HTVL 1 vs 2
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.
How was lentivirus discovered ?
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
Lentiviruses
the prototype virus of this type is visnavirus in sheep
Why were young homosexual males an unusual profile?
It was usually cancer chemo patients or old people
How was AIDS coined as what this was?
Almost all previously described immune deficiency diseases were conenital
Who discovered AIDS?
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
What did further analysis of HIV show?
That the virus is comparatively new and probably originated as a mutant simian virus in central
Africa
Where were the first HIV cases found?
As early as 1939 In Germany (now Poland)
What were AIDS cases related to?
- heterosexual activity, IV drug abuse, hemophilia, transfusion and vertical transmission
NO EVIDENCE THAT CASUAL CONTACT CAN RESULT IN INFECTION
HIV-1A
Mainly spreads heterosexually
-
HIV 1B
- 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
what happens after 8-10 years?
There’s a depletion in CD4 cells resulting in opportunistic infections and also dementia secondary to direct infection of the central nervous system
When do you use the term AIDS?
When the advanced stage of the disease is reached - CD4 count < 200
What about above 200??
Above 200 serology Positive for HIV antibiotics = you have HIV infections ***
What is the count is over 500?
Immunity is normal
Immunosuppressive is directly associated with what?
Immunosuppression correlates inversely to the CD4
Risk to caregivers?
From a needle stick - approximately 1/300 (PEP can be given in these cases)
How does HIV 2 spread?
Heterosexually
What was aids originally called?
gay related immune deficiency
Origins of HIV?
- 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
HIV -like viruses
- 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)
Diagnosis of HIV
HAART - plus aggressive prophylaxis and treatment of opportunistic infections is not curative but the life span of those infected has improved markedly
Biggest risk factor associated with new cases?
IV drug abuse
Natural history of HIV
- 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
Degree of immunosuppression
CD4 counts of < 200 = AIDS
Drops less than 50 = DANGEROUS infection / viruses
