RNA_VIRUSES_(1)(1)[1].pptx

Positive strand RNA viruses
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Coronaviridae
The name "coronavirus" is derived from the
Latin corona, meaning crown
Refers to the characteristic appearance of the
virus under E.M surface projections creating
an image resembling a royal crown
Created by the viral spike(glycoprotein)
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 Genome consists of a single molecule of linear
positive-sense, single-stranded RNA, 27.6–31
kb in size for coronaviruses and 25–30 kb for
toroviruses, the largest known non-segmented
RNA viral genome
 Enveloped
 Genome is infectious
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Diseases:
Middle East Respiratory Syndrome (MERS)
Sever acute respiratory syndrome(SARS)
Common Cold
Avian Infectious Bronchitis
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Middle East Respiratory Syndrome (MERS):
Also known as camel flu
Infects humans, camels and bats
Caused by MERS CoV
enveloped virus containing a 30kb single-
stranded, positive-sense RNA genome
First reported in Saudi Arabia
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Arteriviridae
 The name of the family Arteriviridae is
derived from the disease caused by its type
species, equine arteritis virus
 The genome of arteriviruses consists of a
single molecule of linear positive-sense, single
stranded RNA, approximately 12.7–15.7 kb in
size that includes 9–12 open reading frames
 Genomic RNA is infectious
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Picornaviridae
 Picornavirus virions are non-enveloped,
approximately 30 nm in diameter, and have
icosahedral symmetry
 The genome consists of a single molecule of linear,
positive-sense, singlestranded RNA, 7–8.8 kb in size
 Both the 5’ and 3’ ends of the RNA contain
untranslated regulatory sequences
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 The genomic RNA is polyadenylated at its 3’
end and has a protein, VPg, linked covalently
to its 5’ end
 Genomic RNA is infectious
 Foot and mouth disease virus is one of the
important viruses in the family
 Cytoplasmic replication
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…
Foot and mouth disease virus:
7 distinct serotypes
– Type A
– Type O,
– Type C,
– South African Territories (SAT) 1,
– and Asia 1
No cross protection
Affects Cloven-hoofed animals
Inactivation at pH below 6.5 and above 11
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Astroviridae
• Astroviruses were first described in 1975, when they
were observed by electron microscopy in the feces
of children with diarrhea
• Astroviruses are currently second to rotaviruses in
importance as the cause of gastroenteritis in young
children
• Astroviruses appear to be ubiquitous in young
animals, although they rarely, if ever, cause severe
disease or death, except in birds
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• Astroviruses are so named because the surfaces of
some particles have a distinctive five- or six-pointed
star-like appearance (astron, star)
Negative-stain electron microscopy of Astrovirus
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Negative strand RNA viruses
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Paramyxoviridae
• Enveloped, have prominent envelope
glycoprotein spikes
Viruses included in the group:
Rinderpest Virus
Canine distemper Virus
 Newcastle disease Virus
Measles Virus
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Properties
• No reassortment
• Large in size, more pleomorphic
• 100-300nm
• Antigenically stable
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Rhabdoviridae
• The family contains important animal and human
pathogens, including rabies, vesicular stomatitis, and
bovine ephemeral fever viruses, and several
important rhabdoviruses of fish
Important genera in the family:
Lyssavirus
Vesiculovirus
Ephemerovirus
Novirhabdovirus
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…
• Virions have a distinct rod (bullet) shaped morphology
under electron microscope
• Average diameter of 70 nm and length of 170 nm.
• Members of the family are characterized by their wide host
range.
• Some of Rhabdoviruses are transmitted by arthropods
which may be the original host from which they evolved.
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…
• The genome of Rhabdoviruses is a single
molecule of linear,negative-sense, single-
stranded RNA ranging from 11-15 kb in size.
• Replication of rhabdoviruses occurs in the
cytoplasm of infectedcells.
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Rabis virus
• Rabies virus is a highly fatal disease infects a wide
range of animals and birds.
• The disease occurs throughout the world.
• The number of human deaths due to Rabies was
estimated to be around 50,000 cases annually.
• An estimated 10million person receive post-exposure
treatment against Rabies each year.
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…
• Classification:
– Order: Mononegavirales
• Family: Rhabdoviridae
– Genus: Lyssa virus
• Host affected:
• Rabies virus can infect all warm-blooded animals including
humans, mammals and birds.
• The main susceptible animals are: dogs, foxes,wolves, bats
and raccoons.
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…
Virus properties:
• a) The same characteristics of the family.
• b) Physico-chemical properties:
• The virus is considerably sensitive to physical and
chemical agents due to the presence of
a refractive envelope.
• Temperature:
– heat labile.
• pH :
– Stable at alkaline pH.
• Chemicals
– Sensitive to lipid solvents (Chloroform, ether,
alcohols,..)Sensitive to non-ionic detergents.
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…
Sources of virus:
• Saliva of rabid animals (contains huge amounts of the
virus - 1 ml may carry over million virus particle).
• Contaminated air in the caves containing infected bats.
Pathogenesis:
• Rabies virus enters the body through an animal bite that
deposits the virus deeply in the muscles.
• The virus multiplicate initially in the muscle fibers
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…
• Then gains its entry to the peripheral nerves
through the nerve ending sand travels
centripetally along the neuron to the central
nervous system.
• After multiplication and spread in the brain, the
virus passes again in the cranial nerves to the
adrenal cortex, pancreas and salivary gland.
• The virus mainly excretes in the saliva and
lacrimal secretions.
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Forms of rabies
• There are two clinical forms of the disease:
• Furious form:
– (mostly appear in dogs, cats and equine)
– The animal becomes restless, nervous and aggressive.
– Bites at anything that gains its attention.
– Bites and scratches himself (hyperesthesia).
– Inability to swallow water (Hydrophobia).
– Excessive salivation.
– Exaggerated response to light and sound.
– At the end, animals present the same clinical picture of dump
form.
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…
Dumb (Paralytic) form:
• (mostly appear in humans, ruminants and
Laboratory animals)
– Convulsions.
– Paralysis, coma and respiratory distress.
– Death occurs after 2-14 days from the beginning of
clinical signs..
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Filoviridae
 Filovirus virions are markedly pleomorphic,
appearing as long, filamentous, sometimes branched
forms
 they have a uniform diameter of 80 nm and vary
greatly in length (about 800 nm for Marburg and
1000 nm for Ebola virus)
 Cytoplasmic replication, large intracytoplasmic
inclusion bodies, budding from the plasma
membrane
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Important viruses in the family:
Marburg virus
Ebola viral hemorrhagic fever virus
• Marburg and ebola viral hemorrhagic fevers
are highly lethal and feared zoonotic diseases
• They cause severe hemorrhagic fever in
humans
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Bornaviridae
 Borna disease is named for the town of Borna
in Saxony, Germany
 Usually fatal and neurological disease of
horses and occasionally sheep
 Infection in cell culture characteristically
produces intranuclear inclusion bodies
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Structure
• Spherical envelope
– 90-130nm in diameter
– 8-9 kb genome size
– Replicate in the nucleus
Host range
• Mammals to birds
• Cause Borna disease in horse
• Neurotropic
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Orthomyxoviridae
• Includes viruses with genomes composed of several
(six to eight) segments of ss RNA
• The most important members of the family are the
influenza viruses, which are included in three genera
(Influenzavirus A, B, and C)
• Influenza viruses that are pathogenic to domestic
animals are included in the genus Influenzavirus A,
whereas viruses in the two other genera (B and C)
circulate continuously in humans
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• The name of the family is derived from the Greek
myxa, meaning mucus, and orthos, meaning correct
or right
• The name was intended to distinguish the
orthomyxoviruses from the paramyxoviruses
Virus properties:
 Enveloped, two kinds of glycoprotein spikes which
are hemagglutinin protein and neuraminidase protein
 Genome consists of linear negative-sense, single-
stranded RNA, divided into 6-8 segments, 10–14.6
kb in overall size
*Genetic reassortment occur frequently
*Transcription and RNA replication occur in the nucleus
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Bunyaviridae
 Virions are spherical, enveloped, 80–100 nm in
diameter
 Segmented negative-sense, single-stranded RNA
genome; three segments—L (large), M (medium),
and S (small)—that total 11–19 kb in size
 The S segment of the genomic RNA of the member
viruses of the genus Phlebovirus has an ambisense
coding strategy
 Cytoplasmic replication; budding into Golgi
vesicles
 Genetic reassortment occurs between closely
related viruses
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• The family Bunyaviridae is the largest virus
family, with more than 350 member viruses
included in five genera:
Orthobunyavirus
 Hantavirus
 Nairovirus
Phlebovirus
Tospovirus
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• The family name is derived from the place in
Uganda where the prototype bunyavirus was
isolated
• Viruses in three genera (Orthobunyavirus,
Nairovirus & Phlebovirus) are maintained in
arthropod–vertebrate–arthropod cycles (so-called
arboviruses), which have specificity in regard to
both arthropod vectors and vertebrate reservoir hosts
• This specificity is the basis for the usually narrow
geographic and ecologic niches occupied by each
virus
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Arenaviridae
 Single genus, Arenavirus
 Virions are pleomorphic, enveloped, 50–300
(generally 110–130) nm in size
 Virion contains non-functional host-cell ribosomes
 The family derives its name from the presence
within virions of cellular ribosomes, which, under
thin-section electron microscopy, resemble grains of
sand (arena, sand)
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 Generally associated with rodent-transmitted
diseases in humans
 Viral proteins: nucleoprotein (N), RNA-dependent
RNA polymerase (L), two glycoproteins (Gp1,
Gp2), zinc-binding protein (Z), plus minor proteins
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 Genome consists of two segments, large (L, 7.2 kb)
and small (S, 3.4 kb), of single-stranded RNA
 Most of the genome is of negative sense, but the 5’
half of the S segment and the 5’ end of the L
segment are of positive sense; the term ambisense is
used to describe this unusual genome arrangement
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 Code for four viral proteins in a unique
ambisense coding strategy
 Each RNA segment codes for two viral
proteins in opposite orientation
 the negative-sense RNA genome serves as the
template for transcription of a single mRNA
and the positive-sense can directly be
translated
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 The nucleocapsids are circular as a consequence of
the genomic RNA forming “panhandles”—i.e. non-
covalent bonds b/n conserved complementary
nucleotide sequences at the 3’& 5’ ends of each
RNA genome segment
 Genetic reassortment occurs between closely related
viruses
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Viruses which contain ds RNA genome:
Reoviridae
Birnaviridae
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Viruses under this family:
African horse sickness virus
Blue tongue virus
Rota virus
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Birnaviridae
• Includes viruses with two segments of double-
stranded RNA
• Two members of the family, the agents of
infectious bursal disease of chickens and
infectious pancreatic necrosis of fish are
economically significant pathogens
• Infectious bursal disease was first recognized in
1962 in an outbreak in Gumboro, Delaware i.e.
why infectious bursal disease is called Gumboro
disease
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• The most prominent lesion of this disease is located
in the cloacal bursa (bursa of Fabricius), hence the
present name of the disease
The family Birnaviridae comprises three genera:
• Avibirnavirus - Infectious bursal disease virus
• Aquabirnavirus- infectious pancreatic necrosis virus
• Entomobirnavirus-viruses of inseccts
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Virion properties:
• Non-enveloped, ~ 60 nm in diameter, and having
icosahedral symmetry
• The genome is approximately 6 kbp and consists of
2 molecules of linear ds RNA, designated A & B
• Virions are relatively heat stable, and their
infectivity is resistant to exposure at pH 3 and to
ether and chloroform
• Cytoplasmic replication
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Infectious Bursal Disease / Gumboro
Gumboro small place in Delaware, USA
Highly contagious disease affecting
commercial poultry production worldwide
Caused by infectious bursal disease virus
(IBDV)
There are two distinct serotypes of the virus,
but only serotype 1 viruses cause disease in
poultry
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The virus can survive in a wide variety of
environmental condition (non-enveloped)
Difficult to effectively decontaminate
Can not be degraded by acidic pH or lipid
solvents
Stable enough to live outside the host for 7wks
to 4months(in the straw and sawdust mixture, in
the chicken feed)
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Longevity of selected poultry disease causing
organism in the env’t
Disease causing agent Life span away from birds
Mycoplasma Hrs to days
Avian influenza virus Days to wks
NDV Days to wks
Fowl cholera(pateurella) Wks
Salmonella Wks
Coccidiosis Months
IBDV Months
MDV Months to years
Avian TN Years
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Young chicken (3-6 Wks) are mostly affected
This age with greatest bursal mass =result of
large population of maturing IgM-bearing B-
lymphocytes, the main target of infection
Severe inflammatory changes in the bursa of
Fabricius followed by immuno-suppresion
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Immunosupression:
Predispose the flock to other infection
Negative interference with effective
vaccination
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Transmission:
Infection is via the oro-fecal route, with
affected bird excreting high levels of the virus
for approximately 2 weeks after infection
Feed, water, litter from infected birds remains
infective for significant time period
There is no evidence of vertical transmission
Infected clothing and equipment are means of
transmission between farms
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Host range:
Natural host: domestic fowl (chickens &
turkey)
Wild birds like duck, guinea fowl and
pheasants =naturally infected with IBDV
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Clinical signs:
Disease may appear suddenly and morbidity
typically reaches 100%
Produce a watery diarrhea and may have
swollen feces-stained vent
Most of the flock is recumbent and have
ruffled feathers
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Individual birds show:
Depression
Ruffling of feather
Poor or lack of appetite
unsteady gate
Diarrhea (sometimes bloody)
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Post mortem findings:
Swelling of bursa of fabricus (Edema and
haemorrahge) then shrinks (atrophy) 7-8 days
following infection
Bleeding in the breast and thigh muscle due to
impaired blood clotting
Enlarged kidney and spleen are also typical to
IBDV infection
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Control :
Vaccination of parent breeders and/or young
chicks is the best means of control
 Use of multi vitamin supplement and
facilitating access to water may help
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Viruses which contain ss RNA genome with a
DNA intermidiate
Retroviridae
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Retroviridae
Contain positive sense RNA genome
Use reverse transcriptase Enzyme to copy their
RNA in to DNA
Some the viruses under this family:
Avian leukosis virus
Avian sarcoma virus
Rous sarcoma virus
Bovine leukemia virus
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Feline leukemia virus
Bovine immunodeficiency virus
Equine infectious anemia virus
Feline immunodeficiency virus
Human immunodeficiency virus 1
Human immunodeficiency virus 2
Simian immunodeficiency virus
Visna/maedi virus
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Viruses which contain ds DNA genome with an
RNA intermidiate:
Hepadnaviridae
 Name of family comes from hepa-DNA-virus
 ‘Hepar’ means liver
 As it is Group VII virus, replication involves an
RNA intermediate
 Encodes for an enzyme having reverse
transcriptase activity
 E.g. Hepatitis B virus
Duck hepatitis B virus
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• Hepadnaviruses have small, enveloped, spherical
virions (virus particles) that are about 40–48 nm.
• Double-stranded DNA genome of 3.0-3.4 kb.
• There are two recognized genera of hepadnavirus:
– Orthohepadnavirus - hepatitis B viruses that have been
isolated from mammals
– Avihepadnavirus- consists of hepatitis B viruses that
infect birds
•
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Introduction to bacterial viruses
(bacteriophages)
 Bacterial viruses, known as bacteriophages or phages
(from the Greek phagein, ‘to eat’)
 The genome may be DNA or RNA, single- or double-
stranded, circular or linear, and is generally present as
a single copy
 The majority of phages are tailed
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 Morphology varies from simple, icosahedral and
filamentous phages to more complex tailed phages
with an icosahedral head
 Phages are common in most environments where
bacteria are found and are important in regulating
their abundance and distribution
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Genome structure
o Phage genomes come in a variety of forms and
sizes
o The nucleic acid may be either DNA or RNA
and may be double-stranded or single-stranded
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Single-stranded RNA phages
 Single-stranded RNA phages are small, icosahedral
viruses of the family Leviviridae (from the Latin levis
‘light’)
 Phages in this family have high mutation rates and
some of the smallest RNA genomes known
 They are plus strand viruses (with the genome acting
as mRNA), containing only a few genes, and infect
various Gram-negative bacteria, including E. coli,
Pseudomonas spp. and Caulobacter spp
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 Infecting bacteria by way of sex pillus
Representative example:
 Levivirus serogroup I (e.g. MS2 and f2)
 Allolevivirus serogroup III (e.g. Qbeta, Qβ)
 They comprise major coat (capsid) protein (CP), one
molecule of maturation (A) protein, required for
infectivity and maturation, and a linear ssRNA
genome of about 3500–4200 nucleotides that displays
considerable secondary structure
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Replication cycle of ssRNA phages
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Double-stranded RNA phages
 Phages in the family Cystoviridae (from the Greek
kystis ‘bladder, sack’) contain a dsRNA genome, which
is segmented and packaged in a polyhedral inner
core with a lipid-containing envelope
 Phi6 (ϕ6) was the first member of the family to
be isolated and has been extensively studied
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 The genome comprises three linear segments: RNA L
(large) of about 6400 nucleotides, RNA M (medium)
of about 4000 nucleotides and RNA S (small) of
about 3000 nucleotides
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Major events of replication:
o Phage ϕ6 infects its host, Pseudomonas syringae by way
of the pilus
o Uncoating occurs inside the cell
o virions assemble in the cytoplasm, with their envelope
deriving from the host
o Packaging of the plus strands occurs in the order S–
M–L
o The ss precursors are replicated into mature ds
genomes inside the capsid
o About 100 virions are released following cell lysis
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Single-stranded DNA phages
o There are two groups of ssDNA phages, icosahedral
and filamentous
o Representative icosahedral phages, ϕX174 and S-13
o Icosahedral ssDNA phages belong to the family
Microviridae (from the Greek micros, ‘small’)
o Such phages provided the first evidence for
overlapping genes and revealed the economy of
genetic coding
o Studies on replication of these phages also led to the
discovery of rolling circle replication
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o Filamentous ssDNA phages are in the family Inoviridae
(from the Greek ina ‘fibre, filament’)
o The F specific filamentous (Ff) phages, notably M13,
fd and f1, have been most extensively studied
o They are plus strand phages and are ‘male-specific’,
infecting E. coli strains containing the conjugative plasmid F,
by adsorbing to the tip of the F pilus
o Unlike many other DNA phages, filamentous phages
do not inject their DNA into the host cell; rather
entire phage particles are ingested
o Furthermore, they do not lyse infected cells
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o The genome of the Ff phages is a circular ssDNA
molecule of about 6400 nucleotides
o M13, fd and f1 are 98 percent identical with Ff
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Double-stranded DNA phages
 There is a large variety of dsDNA phages, of which
the T phages and λ have been particularly well
characterized
 T2, T4 and T6 belong to the family Myoviridae (from the
Greek mys, myos, ‘muscle’, referring to phages with
contractile tails)
 T1 and T5 together with λ are members of the
Siphoviridae (from the Greek siphon, ‘tube’, referring to
phages with long, flexible, non-contractile tails)
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 T3 and T7 are in the Podoviridae (from the Greek pous,
podos, ‘foot’, referring to phages with short, non-
contractile tails)
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Structure of Bacterophage T4
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Phage multiplication cycle
1. Lytic or Virulent Phages – They are phages which
can only multiply on bacteria and kill the cell by lysis
at the end of the life cycle
2. Lysogenic or Temperate Phage - They are those that
can either multiply via the lytic cycle or enter a
quiescent state in the cell
 In this quiescent state most of the phage genes are
not transcribed; the phage genome exists in a
repressed state
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 The phage DNA in this repressed state is called a
prophage because it is not a phage but it has the
potential to produce phage
 In most cases the phage DNA actually integrates into
the host chromosome and is replicated along with the
host chromosome and passed on to the daughter cells
 The cell harboring a prophage is not adversely
affected by the presence of the prophage and the
lysogenic state may persist indefinitely
 The cell harboring a prophage is termed a lysogen
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Events Leading to Lysogeny
1) Circularization of the phage chromosome
 Lambda DNA is a double stranded linear molecule
with small single stranded regions at the 5' ends
 These single stranded ends are complementary
(cohesive ends) so that they can base pair and produce
a circular molecule
 In the cell the free ends of the circle can be ligated to
form a covalently closed circle
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Circularization of the lambda chromosome
during the establishment of lysogeny
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2) Site-specific recombination - A recombination event,
catalyzed by a phage coded enzyme, occurs between a
particular site on the circularized phage DNA and a
particular site on the host chromosome
 The result is the integration of the phage DNA into
the host chromosome
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Site-specific recombination during establishment of
lysogeny in bacteriophage lambda
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3) Repression of the phage genome - A phage coded
protein, called a repressor, is made which binds to a
particular site on the phage DNA, called the operator,
and shuts off transcription of most phage genes
EXCEPT the repressor gene
 The result is a stable repressed phage genome which is
integrated into the host chromosome.
 Each temperate phage will only repress its own DNA
and not that from other phage, so that repression is
very specific
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Events Leading to Termination of Lysogeny:
 Anytime a lysogenic bacterium is exposed to adverse
conditions, the lysogenic state can be terminated. This
process is called induction
 Conditions which favor the termination of the lysogenic
state include: desiccation, exposure to UV or ionizing
radiation, exposure to mutagenic chemicals, etc
 Adverse conditions lead to the production of proteases
(rec A protein) which destroy the repressor protein
 This in turn leads to the expression of the phage genes,
reversal of the integration process and lytic multiplication
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Termination of lysogeny in bacteriophage lambda by
inactivation of the repressor and excision of the prophage
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Application of Bacteriophages
Decontamination of the environment, such as in
purifying water supplies
Might be used to combat pathogenic bacteria
Typing of bacterial strains of medical interest
Some temperate phages contribute ‘lysogenic
conversion genes’, for example diphtheria or cholera
toxin genes, when they establish lysogeny, thereby
converting the host to virulence
Used as cloning vectors
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Reading assignment
• Newly emerging and re-emerging DNA and
RNA viruses?
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Prions
 Named for their description as "proteinaceous and
infectious particles’’
 Lack any detectable nucleic acids or virus-like
particles
 They resist inactivation procedures that normally
affect nucleic acids
 A prion is an infectious agent composed of protein
in a misfolded form (they are infectious proteins that
cause fatal neurodegeneration in humans and
animals)
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 Prion infectivity is remarkably heat resistant and
some infectivity can survive autoclaving for
prolonge periods
 Prion infectivity is also very resistant to
inactivation by irradiation and by some chemicals
that inactivate virus infectivity
 Treatments that are used to inactivate prion
infectivity include exposure to 2.5–5 per cent
sodium hypochlorite solution or 1 M NaOH for
1–2 hours
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 Prion diseases = transmissible spongiform
encephalopathies
 All known prion diseases affect the structure of the
brain or other neural tissue and all are currently
untreatable and universally fatal
 In 2013, a study revealed that 1 in 2,000 people in
the United Kingdom might harbour the infectious
prion protein that causes vCJD
 Prions are not considered living organisms but may
propagate by transmitting a misfolded state
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 If a prion enters a healthy organism, it induces
existing, properly folded proteins to convert into the
disease-associated, prion form; the prion acts as a
template to guide the misfolding of more proteins
into prion form
 Note that the propagation of the prion depends on
the presence of normally folded protein in which the
prion can induce misfolding
 Animals that do not express the normal form of the
prion protein can neither develop nor transmit the
disease
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 The altered structure is extremely stable and
accumulates in infected tissue, causing tissue
damage and cell death
 This structural stability means that prions are
resistant to denaturation by chemical and physical
agents, which makes disposal and containment of
these particles difficult
 They are also resistant to endogenous proteases,
which is the key to its accumulation into aggregates
8/20/2022 106

 All known mammalian prion diseases are caused by
the so-called prion protein, PrP
 The endogenous, properly folded form is denoted
PrPC (for Common or Cellular)
 The disease-linked, misfolded form is denoted PrPSc
(for Scrapie, after one of the diseases first linked to
prions and neurodegeneration)
 PrPC is a normal protein found on the membranes of
cells
 It has 209 aa (in humans), one disulfide bond, a
molecular mass of 35–36kD and a mainly alpha
helical structure
8/20/2022 107

 PrP has been reported to play important roles in cell-
cell adhesion and intracellular signaling in vivo, and
may therefore be involved in cell-cell
communication in the brain
 PrPSc the infectious isoform of PrP
 PrPSc, is able to convert normal PrPC proteins into
the infectious isoform by changing their
conformation, or shape
8/20/2022 108

 Prions cause neurodegenerative disease by
aggregating extracellularly within the CNS to form
plaques known as amyloid, which disrupt the normal
tissue structure
 This disruption is characterized by "holes" in the
tissue with resultant spongy architecture due to the
vacuole formation in the neurons
 Other histological changes include asterogliosis and
the absence of an inflammatory reaction
8/20/2022 109

 Incubation period for prion diseases is relatively
long (5 to 20 years)
 However once symptoms appear, the disease
progresses rapidly, leading to brain damage and
death
 Neurodegenerative symptoms can include
convulsions, dementia, ataxia (balance and
coordination dysfunction), and behavioural or
personality changes
8/20/2022 110

 All known prion diseases, collectively called
transmissible spongiform encephalopathies (TSEs)
 They are untreatable and fatal
 Many different mammalian species can be affected
by prion diseases, as the prion protein (PrP) is very
similar in all mammals
 Due to small differences in PrP between different
species it is unusual for a prion disease to transmit
from one species to another
8/20/2022 111

 The human prion disease variant Creutzfeldt-Jakob
disease, however, is believed to be caused by a prion
that typically infects cattle, causing Bovine
spongiform encephalophaty and is transmitted
through infected meat
8/20/2022 112

Diseases caused by prions
 Sheep & goat: Scrapie
 Cattle: Bovine spongiform encephalopathy (BSE) or
mad cow disease
 Mink: Transmissible mink encephalopathy (TME)
 White-tailed deer, elk, mule deer, moose: Chronic
wasting disease (CWD)
 Cat: Feline spongiform encephalopathy (FSE)
 Nyala, oryx, greater kudu: Exotic ungulate
encephalopathy (EUE)
 Ostrich: Spongiform encephalopathy (Has not been
shown to be transmissible)
8/20/2022 113

Human:
Creutzfeldt-Jakob Disease(CJD)
latrogenic Creutzfeldt–Jakob disease (iCJD)
Variant Creutzfeldt–Jakob disease (vCJD)
 Familial Creutzfeldt–Jakob disease (fCJD)
 Sporadic Creutzfeldt–Jakob disease (sCJD)
 Gerstmann–Sträussler–Scheinker syndrome (GSS)
Fatal familial insomnia (FFI)
Kuru
8/20/2022 114

Scrapie:
 Disease of sheep and goats
 Many affected animals scrape against hard objects
such as fence posts, hence the name of the disease,
and many grind their teeth, stumble and fall; all
eventually die
8/20/2022 116

Fig. Prion proteins (shown in red in mouse brain cells) can disrupt traffic
in the thread like axons of nerve cells, leading to death of the cells
8/20/2022 117

Prions:
o Misshaped versions of a normal brain protein
o Clump together in large aggregates that are
hallmarks of degenerative brain disease
o Clumps of these proteins may contribute to
nerve death by causing mitochondria to crash
o Clumps of misfolded proteins cause traffic jams
in brain cells
8/20/2022 118

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