virology: prions and tumor viruses Flashcards
Prions
- Infectious proteinaceous particles without nucleic acid
- Abnormal folding of a normal glycoprotein
- Implicated in fatal neurodegenerative disease with long incubation periods
- Non-immunogenic and extremely resistant to inactivation
- Neuropathological changes include vacuolation of neurons and neuropil
transmissable spongiform encephalopathy (TSE) nomencalture
PrPc is a native protein with an α-helical structure
The protein is present in normal cells including lymphocytes and neurons
When PrPc interacts with PrPs, through ingestion or injection, PrPc is converted to an abnormal form with a β-sheet conformation
PrPsc is protease resistant and accumulates in neurons
Neuronal accumulation results in vacuolation and development of neurologic signs
forms of transmissible spongiform encephalopathy (TSE)
Transmissible
* Typically occurs by exposure to an external source
* Ritualistic cannibalism in the Fore people in Papua New Guinea resulted in Kuru
Sporadic
* Random sporadic conversion of PrPc to PrPsc results in sporadic Creutzfeldt-Jakob (CJD) disease in humans
Familial
* Mutation in the PrP gene results in abnormal folding in Gertsmann-Straussler-Scheinker syndrome
Scrapie
Prion dz
* Insidious, fatal neurologic disease of adult sheep and goats
* Long incubation period means that it is typically seen in breeding aged sheep
* Clinical signs include restlessness or nervousness, pruiritis leading to loss of wool, emaciation, and death within 6 months
* Histologically there is no inflammation, only vacuolation of neurons in the medulla with vacuolation of the neuropil and astrocytes
bovine spongiform encephalopathy (BSE)
prion dz, mad cow dz
* not species specific
* Molecular strain typing showed the Creutzveldt-Jakob (human, vCJD) and BSE prions to be identical
* The epidemic was attributed to feeding meat and bone meal including offal as a protein source to cattle
* There is no horizontal transmission
* Clinical signs include ataxia, hypermetria, and the tendency to fall
Control measures in the US include
* Incineration of all small ruminant carcasses
* Incineration of brains and spinal cords of cattle older than 30 months of age
chronic wasting disease
TSE (prions) of elk, mule deer, white-tailed deer, and moose
Clinical signs are chronic weight loss, behavioral changes, ataxia, tremors leading to death
Transmission is thought to be by fecal contamination of grass or in utero
retroviruses
Labile enveloped RNA viruses
* Requires exchange of blood or close contact for transmission
Contain a reverse-transcriptase which transcribes viral RNA into double-stranded DNA
* RNA-dependent DNA polymerase
* No proof-reading results in a high mutation rate
Double-stranded DNA is integrated as a provirus into the host chromosomes
* Insertion into the genome is random
* Site determines the outcome of cellular changes
endogenous vs exogenous retroviruses
Endogenous
* Widespread in mammals
* Can constitute as much as 10% of the host genome
* Transmitted across the germ-line (vertical transmission)
* Usually silent but can recombine with exogenous retroviruses
Exogenous
* Capable of horizontal transmission
oncogenic retroviruses
Alpha-, Beta-, Gamma-, Delta-, and Epsilonretrovirus
Induce neoplastic transformation in cells they infect
Slowly-transforming
* Induce B-cell, T-cell, or myeloid tumors after long incubation periods
* Provirus must be inserted close to a cellular oncogene
* Interferes with the regulation of cell division
Rapidly transforming
* Induces tumors after short incubation periods
* Contains a viral oncogene
slowly transforming oncogenic retroviruses
Induce B-cell, T-cell, or myeloid tumors after long incubation periods
Provirus must be inserted close to a cellular oncogene
Interferes with the regulation of cell division
rapidly transforming oncogenic retroviruses
Induces tumors after short incubation periods
Contains a viral oncogene
Feline leukemia virus
Gamma retrovirus (Labile RNA enveloped)
* Most clinical FeLV infections manifest as anemia or immunosuppression
* Other possible clinical disease includes tumors, hematologic disorders, immune-mediated disease, neuropathy, reproductive failure, fading kitten syndrome
* The clinical disease is often associated with host factors (like age) and the subgroup of the virus
* The virus targets cells that are mitotically active
* Tumors occur due to insertional mutagenesis and recombination with a variety of proto-oncogenes
* FeLV isolated from thymic lymphomas are replication defective
FeLV subgroups
FeLV contains 4 subgroups (A, B, C, and T)
* **All FeLV positive cats have FeLV A **
* Other subgroups arise from FeLV A through mutation
* Cats infected with FeLV A and B have a higher risk of developing tumors than those with FeLV A alone
* FeLV A and C isolates result in fatal anemia
* FeLV T is a T-cell tropic, cytopathic virus and FeLV A and T results in immune deficiency
FeLV A subgroup
all FeLV positive cats
mutates into other subgroups
FeLV B subgroup
has A and B
higher risk of tumors
