Proteinaceous infectious agents
prions
Prions induce a conformational alteration of a normal ____ protein from what to what?
CNS protein
from alpha helix to beta pleated sheets
Prions are _________ protein aggregates that cause extensive _________ of neurons and produce fatal degenerative CNS diseases called what?
insoluble
vacuolation
transmissible spongiform encephalophaties
What does spongiform refer to?
Presence of multiple vacuoles that make the tissue look like a sponge
What is the normal prion protein called? What is the infectious form called?
PrPc
PrPsc
What are normal prion proteins?
Surface components of neurons and glial cells
What makes prions so hard to eradicate?
Very resistant to inactivation
Where was Kuru endemic to?
How did people get it?
How did it stop?
Papa New Guinea
Engaged in ritual cannibalism - ate the liver and brain of esteemed person
stopped when they stopped eating people
Which is the rapid variant of TSE?
CJD
What is the sheep TSE called? Why is it aptly named?
Scrapie
Infected sheep scrape along fences and walls
What symptoms does kuru produce? How is it transmitted?
spasticity and ataxia - infectious
Extinct
What symptoms does CJD produce? how is it transmitted/acquired?
dementia, spasticity, seizures
infectious or inherited
What does most forms of human TSEs have in common in terms of symptomology?
Most have ataxia as a feature
What is the enzyme that retroviruses must carry with them?
RNA dependent DNA polymerase or reverse transcriptase
What is the central dogma of molecular biology?
DNA –> RNA –> protein
How do retroviruses integrate their genome if they have RNA?
RNA –> reverse transcriptase –> dsDNA –> integrate into host genome
When the DNA is integrated into the host genome, what is the retrovirus now called?
a provirus
When the provirus chooses to replicate, how does it accomplish this?
Uses host RNA polymerase to synthesize mRNA to manufacture viral protein, synthesize reverse transcriptase and makes its genome (ssRNA)
What are the two big families of retroviruses?
Oncoviruses
Lentiviruses
HIV-like viruses infect many animals without causing disease - e.g. monkeys. In what animals does it cause disease?
Equines and house cats (and humans)
From what was SIV first isolated?
Japanese macaques
What are the three different SIV variants?
SIVgm - green monkeys
SIVcpz - chimpanzee
SIVsm - sooty mangabey
Why do we believe that HIV came from chimps?
SIVcpz found in Gabon serologically reacts with HIV-1
How do we believe that HIV entered the human population?
Entered human population through bush meat trade in Africa, then sexual transmission
What did SIVcpz probably evolve into to infect humans?
HIV-1 and HIV-0
Which SIV serotype has 80-90% homology with HIV-2?
SIVsm
What is the approximate period of incubation of HIV?
10 years
How is HIV-2 different from HIV-1?
Low lethality, mainly in West Africa and incubation period closer to 20 years
How did HIV go from Africa to Europe?
Cameroon was originally a german colony. After WW2, this colony was forced to leave and go back to Germany (then Danzig - now Poland), brought HIV with them
P. ________ is characteristic of AIDS.
P. jiroveci (used to be called P. carinii)
P = pneumocystic
What ultimately led to the discovery of HIV?
Found a high order of pentamidine to treat PCP (P. cariini pneumonia) in young, gay males - also high rates of Karposi Sarcoma at the time - noticed they were immunosuppressed and termed cause as GRID (now HIV)
What does GRID stand for?
Gay-related immune deficiency
Where is HIV huge? What is it considered in terms of public health?
What is a major issue for treatment?
West, east and south Africa
Pandemic
Affordability
Soon after infection with HIV, what symptoms manifest? What is it associated with?
Flu-like illness which is associated with seroconversion
What is seroconversion?
Period in which HIV antibodies are produced
How many years does it take for immunosuppresion to develop?
years to decades
What does HIV cause after a period of years?
CD4 cell depletion resulting in opportunistic infections and also dementia secondary to direct infection of CNS
AIDS is reserved for who?
those with a CD4 count lower than 200 cells
What is the normal range for CD4 cells?
1500-500
Role of cofactors in accelerating the development of AIDS is controversial, but certain __________ appear to have roles.
mycoplasmas
What are the different types of people infected with HIV?
non-progressers - infected with HIV but remain perfectly healthy
rapid progressors - CD4 count depletion within shorter time frame (~3 years)
HIV resistant - despite repeated exposure, no seroconversion
Is it possible to completely eliminate HIV?
yes, with 50+ years of HAART
What is the staple treatment for keeping HIV in check?
HAART - highly active anti-retroviral therapy
What is an issue with HAART?
very expensive
At what CD4 count does a person basically have normal immunity?
What is an HIV CD4 count where opportunistic infections may become a problem?
500+
499-200
(although not definite numbers, some people can be better with less, some worse with more)
What is the Kaposi sarcoma AIDS defining agent?
Human herpes virus 8
How is HIV transmitted?
heterosexual sex, needle sharing for IV drugs, hemophelia treatment, blood transfusion, homosexual sex as well
What is the risk to caregivers after a needle prick?
1/300
How acn the seroconversion rate of accidental healthcare exposure be decreased?
with PEP - post-exposure prophylaxis (combivir + Kaletra)
What may ultimately be one answer to the HIV pandemic?
HIV vaccines