Poxviruses and Prions

fast facts about poxviruses

enveloped, huge, complex, large dsDNA genome, chemical composition resembles that of a bacterium

what percentage of vaccinia virus (poxvirus) is protein, lipids, and DNA

90% proteins, 5% lipids, 5% DNA

how many structural polypeptides have been detected in poxvirus particles?

more than 100

what are examples of human poxviruses?

variola (smallpox), molluscum contagiosum (molluscum)

what are examples of animal poxviruses?

vaccinia, cowpox, orf (sheep pox), mpox (monkey pox that can also infect humans now)

what is the structure of poxviruses?

complex, ovoid symmetry, relatively large compared to other viruses

envelope and outer membrane surround core, core (nucleocapsid) contains viral genome, viral proteins and enzymes

viral genome: large (120kb), dsDNA

t/f poxvirus virions are not resistant to environmental inactivation and drying agents even though it has an envelope, BUT standard disinfectants will not inactivate it

false- opposite (are highly resistant to enviro inactiv but standard disinfct will inactivate)

what does the replication cycle of a poxvirus include?

bind to cell surface receptors and enter by fusion

virion core contains all enzymes required for transcription

viral DNA polymerase is synthesized

after DNA replication structural proteins are made and virus particles are assembled in cytoplasmic inclusion bodies

envelopes are composed of viral proteins (not derived from host cell membrane)

most virus is released by cell lysis, but some are released by exocytosis

what is unique about poxviruses?

only known DNA virus that replicate entirely in the cytoplasm and their envelope is made of viral proteins, not host cell membrane

t/f poxviruses are infectious during the incubation period of infection

false

what are clinical manifestations of poxvirus infection?

respiratory virus infected upper respiratory tract, second viremia produces rash

what is the mortality rate of variola major versus variola minor?

15-40% versus 1%

when did we stop routinely vaccinating for smallpox and who still gets vaccinated for it?

1985

only designated military personnel and lab researchers working on certain poxviruses

what are the 2 licensed vaccines for smallpox and mpox?

an attenuated, non-replicating strain of modified vaccinia virus

a replication competent vaccinia virus vaccine

what is done about smallpox, mpox, and vaccinia vaccine complications?

FDA approved drugs that can be used to treat complications, vaccinia-immune human globulin may be used when vaccine complications occur

prion

proteinaceous infectious particle, agents of a group of chronic diseases called prion diseases or transmissible spongiform encephalopathies (TSE), infect the nerve tissues of animals and humans, manifest with long incubation periods lasting up to decades, composed solely of protein (no nucleic acid), self replicating, much more resistant to inactivation by UV and heat than viruses, highly resistant to formaldehyde and nucleases, can be inactivated by hypochlorite, sodium hydroxide, and autoclaving

do prions, viruses, or both contain nucleic acids?

viruses only

do prions, viruses, or both contain protein?

both, prions have cellular and viruses have viral

are prions, viruses, or both inactivated rapidly by UV light or heat?

viruses only

what do prions look like under an electron microscope?

filamentous rods

what do viruses look like under the electron microscope?

icosaheadral/complex/helical

does infection by prions, viruses, or both induce antibodies?

viruses only

does infection by prions, viruses, or both induce inflammation?

viruses only

PrP^c

a membrane bound protein found mostly on the surface of neuronal and non-neuronal cells, it is the native form of the protein (normal constituent of healthy tissues), exists primarily in the alpha helical conformation, sensitive to degradation by protease

PrP^SC

protease resistant, aggregates into amyloid like rods, and accumulates within cells in vacuoles and lysosomes, exists primarily in a beta helical conformation

what are the steps of prion replication?

PrP^C produced by cells is secreted to the cell surface

PrP^SC may be acquired or produced by an altered PrP^C gene

PrP^SC reacts with PrP^C on the cell surface

PrP^SC converts the PrP^C to PrP^SC

the new PrP^SC converts more PrP^C

the new PrP^SC is taken in by endocytosis

PrP^SC accumulates in endosomes

PrP^SC continues to accumulate as the endosome contents are transferred to lysosomes, the result is cell death

kuru

fatal neurological disease first described in societies in Papua New Guinea involved in cannibalism, it is no longer prevalent because this practice has stopped, prion induced disease

cretzfeldt-jakob disease

globally prevalent, rare, chronic encephalopathy, 10% of cases are familial and carry the mutated prion gene, onset is middle to late life (40-60s), clinical course lasts for 7-18 months

vCJD is a new disease that is associated with intake of BSE contaminated beef and beef products, mainly in northern europe/UK

BSE

bovine spongiform encephalopathy

gerstmann-straussler-scheinker disease (GSS)

extremely rare, inherited, neurodegenerative brain disorder, disease usually begins between the ages of 35-55, symptoms include dysarthria, nystagmus, spasticity, visual disturbances sometimes leading to blindness

fatal familial insomnia

rare genetic condition that causes sleeping difficulties, memory loss, and involuntary muscle twitching, condition gets worse overtime and its life threatening, no cure but treatment can temporarily slow the progression of symptoms

what are some oral manifestations of human transmissible spongiform encephalopathies?

dysphagia (difficulty in swallowing), dysarthria (difficulty in speaking because the muscles used for speech are weak), paresthesia (tingling, prickling, or numbness), orofacial dysesthesia (abnormal sensations in the absence of stimulation)

t/f the US and UK have differing opinions on transmission risks of prion diseases

true- US is more strict, special precautions should be taken in addition to standard ones when treating known CJD or vCDJ patients

what are some steps that should be taken when treating CJD/vCJD or patients at risk (recipients of dura mater grafts, pituitary hormone injections before mid 1980, and those with family members with a history of CJD)?

use disposable instruments or sterilize instruments for 18 min in a vacuum autoclave, keep instruments moist until cleaned and decontaminated, water supply should be independent using a stand alone suction unit or infusion, treat the patient at the end of the day

Which statement regarding prions is TRUE?

A. Prions are mutated viral proteins that are resistant to proteases.

B. Humans acquire prion diseases solely by eating contaminated beef.

C. Prions replicate by converting a normal cellular protein to an abnormal conformation.

D. The nucleic acid genome of prions is resistant to nucleases.

E. Prion diseases are rarely fatal.

C. Prions replicate by converting a normal cellular protein to an abnormal conformation.