Picornaviridae Togaviridae Arenaviridae Flashcards
Morphology and Structure of Picornaviruses
Virion: non-_________, _____, (23-25 nm), __________ symmetry
* Genome:
– (___Ve) sense RNA, 7.2-8.4 kb
* RNA is _________
– Ten genes, eleven proteins (poliovirus)
* VP1, VP2, VP3, VP4 structural proteins
– VP____ interacts with viral RNA
* 2A, 2B, 2C proteases
* 3A, 3B, 3C, 3D RNA replication
– __________ replication
enveloped, small, Icosahedral, +, polyadenylated, 4, Cytoplasmic
Picornaviruses
Morphology and Structure of Picornaviruses
Members of the Picornaviridae Cause Many Serious Diseases
of Man and Animals
1. Genus Apthovirus
- ____ and _____ disease, most destructive in Africa
2. Genus Rhinovirus
- cause ______ tract infections, acid labile, cause _____ in humans (110 types) and pigs
3. Genus Enterovirus
- _______ type member, 3 major types cause paralysis
4. Genus Hepatovirus
- Hepatitis __, contagious ___ infections
5. Genus Cardiovirus
- ____ group, cause ____ and ____ inflammation, acid labile, source is a ____ reservoir
Foot, mouth, respiratory, colds, Poliovirus, A, liver, EMC, heart, brain, rodent
A Phylogenetic Tree of the Picornaviridae
General properties of Picornaviruses
Hepatitis = inflammation of liver, multiple causes
In viral hepatitis: ABCDEF
Hepatitis E = zoonotic virus, transmitted from pigs to humans
Genome structure and organization of Picornaviridae
How can we use/maximize benefits from genetic material?
Structural proteins = 5’ end
no structural = 3’ end
Can crop genome organization, put under one another
Vp4, etc encode P1
What encodes P2 and P3?
Genome structure and organization of Picornaviridae
Picornavirus Members Bind to Many Different Host Receptors
Car = coxaci adenovirus receptor
Virus uses receptors to enter cell
I am-1, Vcam-1, CD55
Replication of Picornavirus RNA
Positive sense RNA virus
Review replication of positive sense viruses
Lipid bilayer structure
Bottom left picture: receptor and key have to match in order for virus to enter
Geographical distribution of Foot and Mouth Disease
Family
Genus
7 distinct serotypes
Not cross protective = one vaccine agonist and one strain will not protect against other strains
Memorize names
Carribbean, Oceania, north and Central America = free b/c strict control measures.
FMDV-Host Range
All _________-_________ domestic animals including:
Most _______-footed wild animals:
cloven, hoofed
-Cattle
Buffalo
-Sheep
-Goats
-Swine
cloven
-Deer
-Bison
-Feral hogs
-Antelope
Armadillos are not only ________ but are capable of transmitting ______ to ___________ and _____ species of animals. FMDV is not reported in _____-toed animals such as as?
INSERT picture from this slide
susceptible, FMDV, each other, other, Odd, Horses, Zebras and Rhinos
Some epidemiological hints-FMDV
1. __________ 100% in susceptible animal population located in the U.S., Canada, Mexico, others.
2. _________ less than 1%
- Higher in _______ animals and highly _______ virus strains
- Animals generally _________ to prevent spread (e.g. incineration)
Incubation period depends on which _____ of FMD virus (___ serotypes), _______, and the route of ____. Can be as short as __-__ days in close contact or as long as ___-___ days from windborne
infection. Experimentally shown to be as short as?
Morbidity, Mortality, young, virulent, destroyed, strain, 7, dosage, entry, 2-3, 10-14, 18-24 hour
Worldwide distribution of FMDV
Get notes
FMDV-Clinical Signs
Incubation period: 2 to 14 days
** ____ and _____
** Feet, mouth, nares, muzzle, teats
Progress to erosions
Lameness, reluctance to move,
sloughing of hooves
Abortion
Oral lesions (vesicles)
Tongue, dental pad, gums, soft
palate, nostrils, muzzle
** Excess _______, _____, nasal _____
** ____, ____ of body condition
Erosion and ulceration on the teat
of the udder
Death in young animals
Fever, vesicles, salivation, drooling, discharge, Lethargy, loss
FMDV-Clinical Signs cont…
Post photos
Sloughing of hoof —> regeneration occurring; occurs in severe cases
Hard palate, interdigital space.
Transmission of FMDV
Entire chart
Temporal progression of foot-and-mouth disease (FMD) in naïve and vaccinated cattle
See difference between pattern of disease in vaccinated versus unvaccinated
FMDV-Clinical Signs: Sheep and Goats
Mild form
Fever, Lameness
Erosion and ulceration in the mouth
This one
FMDV
Epidemiology of FMDV
Recovered animal good immunity for awhile
Death/slaughter
FMDV-Post Mortem Lesions
Single or multiple vesicles
Various stages
of development
White area, 2mm-10cm
***____ filled blister
Red erosion, fibrin coating
Dry lesions
Sloughed hooves
____ heart appearance = image **
fluid, Tiger
FMDV-Laboratory Diagnosis
________ diseases are clinically indistinguishable!
Suspect animals with ______ or ______ and vesicles
Tranquilization may be necessary
Laboratory testing essential
Vesicular, salivation, lameness
Ante mortem sample: saliva b/c rich in virus since it is secreted in saliva
Post mortem sample:
Principles of FMDV diagnosis
This slide
Differential diagnosis of Vesicular diseases based on the naturally occurring
diseases in different domestic species of animals
Highlighted portion
R = resistant
S= susceptible
Study
Clinical Comparison: Snout in pigs
Morphology differs between types
Clinical Comparison: Feet
Differential Diagnosis of FMDV in various animal species
Put family
Porcine enteroviruses (PEVs)
______ disease
______ disease
Reproductive diseases porcine enteroviruses
- **Two distinct serotypes (PEV___ and ___) was first reported in 1979
- It is associated with the _______ strain of porcine enterovirus, serotype PEV___
- Most infections with porcine enteroviruses, which belong to the
family _________, cause no apparent disease, but some strains are capable of
causing ** ___________: (**_____ and _______) - Reproductive disorders (stillbirths, foetal mummification, embryonic death and
infertility
Teschen, Talfan
9, 10, neurotropic, 1 Picornaviridae, polioencephalomyelitis, Teschen and Talfan
PEV - Pigs with _________ paralysis, adopts a ____-sitting posture
Put image
posterior, dog
Encephalomyocarditis virus (EMCV)
* EMCV is resistant to many environmental conditions and remains stable
at pH 3–8
* EMCV has a broad host range and has been isolated in over 30 species of
mammals and birds.
* Rodents are thought to be the reservoir species.
* In neonatal pigs, mortality rates can reach ____%
* Pig-to-human transmission has not been documented
* Ingestion, either of EMCV-infected carcasses (rats or mice) or of
food/water contaminated by infected carcasses, is thought to be the
primary route of transmission in swine. Direct pig-to-pig transmission has
not been demonstrated.
* Sudden death can occur in _______. Lethargy, fever, anorexia, dyspnea,
vomiting, and paralysis
100, neonates
FMDV disease in Humans
Very low incidence
40 cases since 1921
Most reports ended when FMD was eradicated in _____
NOT a public health concern
Incubation period: 2 to 6 days
Clinical signs
Mild headache, malaise, fever
** _____, ______ sensation of fingers, ____, ____ prior to _____ formation
Clinical disease rare
** Infected by ____ contact, ingestion of unprocessed ___/____ products
** Type ___, __, rarely A
Transmit virus to animals
Rarely harbor virus in respiratory tract for 1-2 days
*** Low risk of _______ carriage
Contaminated boots, clothing, vehicles
Europe, Tingling, burning, palms, feet, vesicle
direct, milk, dairy, O, C, prolonged
FMDV-Vaccination
Killed vaccine, serotype specific
North American Foot-and-Mouth Vaccine Bank
______ ______, NY
Monitor disease outbreaks worldwide
Stock active serotypes and strains
Essential to isolate virus and identify the serotype to select
correct vaccine
**FMD ___ vaccine: Aftovac pure
** _______ Vaccine: Aftovax
- vaccinate only healthy animals
Plum Island, VRI, Inactivated
Features of ideal FMDV vaccines
Recommended actions in FMDV outbreaks
Confirmatory diagnosis
_________
Must properly destroy exposed?
Products:
2% sodium hydroxide (lye)
4% sodium carbonate (soda ash)
5.25% sodium hypochlorite
(household bleach)
0.2% citric acid
Areas must be free of organic matter
for disinfectants to be effective
Depopulation, cadavers, litter, animal products
Bovine enterovirus (BEV)
** Belongs to the genus __________
** ____ (18–30 nm), non-_______ viruses with an ________ capsid
** Only two serotypes, BEV-__ and BEV-__ are now
recognized
* Isolation of BEV from feces and various tissues
from apparently healthy animals or from animals
with clinical signs that ranged from mild to
moderate diarrhea to reproductive disease
*** Sometimes the mucosa of the ____ _______ and ______ had multiple foci of _______ and _____
* Virus isolation from intestinal lesions followed by
electron microscopy yielded an approximately 27
nm, nonenveloped, cytopathic, virus
Enterovirus, Small, enveloped, icosahedral, 1, 2, spiral, colon, cecum, hemorrhage, ulceration
**Avian encephalomyleits virus (AEV) OR __________ ________ ___
* Viral infection of the _______ system of many _____ birds, chickens, turkeys, quail, pheasants, and pigeons
** Causes ______ manifestations such as ataxia, tremors, and paralysis
* Vertical and horizontal transmissions have
been documented.
* Microscopic lesions in the CNS in the
brain (cerebral peduncle, cerebellum, brain
stem) and spinal cord
* Degeneration and necrosis of _____,
perivascular lymphocytic cuffing, and
gliosis with the formation of glial nodules
*** __________ of neurons in the ________ _______ = AEV
Tremor virus A, nervous, naive, nervous, neurons, Chromatolysis, medulla oblongata
Picture for AEV
AEV strain classification and Pathogenicity
**Pathotype-I: presented by _____ ___ strains: enterotropic
*** These strains infect chickens readily via the ____-____ route, multiply
in the intestine, and shed in feces.
**** Pathotype-II: ______-adapted strains constitute the other pathotype
** They do not infect via the oral route except with very ___ dose, and do not spread _____
*** _________ accumulations occur in viscera, particularly the ________ is characteristic
natural, field, oral-fecal, Embryo, high, horizontally, Lymphocytic, pancreas
Duck Viral Hepatitis (DVH
** (DVH) is an acute, highly contagious, viral disease typically affecting __________ less than six weeks of age
** Short incubation period, sudden onset, high mortality, and characteristic liver lesions
** should not be confused with duck hepatitis B virus (Hepadnaviridae)
*** DHAV-1: now classified in the genus _____________
** Two antigenically distinct genotypes have been identified in Taiwan (DHAV-___) and identified in China and South Korea (DHAV-____).
***** DVH propagated in chicken and duck embryos, and they do not produce hemagglutinins
ducklings, Avihepatovirus, 2, 3
In cases of duck viral hepatitis virus, the _____ is enlarged and covered with _______ foci up to 1 cm in diameter
** Spleen may be _____ and ______.
** Kidneys may be ______, and renal blood vessels ______
Liver, hemorrhagic, enlarged, mottled, swollen, congested
Picture of DVH
Equine Rhinitis virus
* The equine rhinitis-A virus and the equine rhinitis-B virus
** Rhinovirus, differentiating _____ groups according to their
characteristics: equine rhinovirus-1,equine rhinovirus-2, equine
rhinovirus-3 and **_____-stable equine picornavirus
*** Later the equine rhinovirus type ___ was renamed Equine Rhinitis A Virus (ERAV), being classified within the genus Aphthovirus, the other three were included in a new genus called *** ________
Considering three serotypes of Equine Rhinitis B Virus(ERBV-1, ERBV
-2, and ERBV-3).
* Isolated from oral and nasopharyngeal secretions, plasma and urine
*** Main route of excretion seems to be urine
*** Clinical signs: fever (1 to 3 days), anorexia, serous to mucopurulent
nasal discharge, ________, _______, cough, and ___________.
** Diagnosis can be carried out directly by demonstrating the presence of
the virus through viral _______ or detection of viral ____ by RT- PCR from nasopharyngeal swabs or urine in the case of ERAV
***** ___________: indirectly detecting increased specific antibodies
against these viruses.
four, acid, 1, Erbovirus, pharyngitis, bronchitis, lymphadenopathy, isolation, RNA, Seroconversion
Equine Rhinitis virus
Picornaviruses infect humans
Large number of viruses cause Hepatitis syndrome. Hepatitis A, B, C, D, and F.
Hep E is most important for us b/c it is zoonotic. Transmits from pigs, especially animals that eat liver and sausage, if transmitted can be transmitted to humans.
Poliovirus
**-Principally an infection of the __________ tract
-Most people who get infected with poliovirus (about 72 /100) will
not have any visible symptoms
**-About 25% with poliovirus infection will have ___-like symptoms
**-Very contagious and spreads through _____-to-_____ contact
**Clinical spectrum
-Abortive poliomyelitis
-Fever, malaise, headache, vomiting, etc.
-Resolves in about a week
**Nonparalytic poliomyelitis (an aseptic meningitis)
-Similar symptoms, but also back pain
-Paralysis can occur in a small percentage of cases
Paralytic poliomyelitis
-Motor neuron damage
-Mostly flaccid paralysis, but spasms in some
-Recovery within 6 months, otherwise permanent
**Progressive postpoliomyelitis muscle atrophy
(postpolio syndrome)
Can appear decades after polio infection
gastrointestinal, flu, person, person
Poliovirus
Disappearance of Polio in the USA
* Children under 5 years are more susceptible to
Poliovirus infection
* Two types of Poliovirus vaccines
** Inactivated Polio-vaccines (IPV): ____ vaccine
*** Oral Poliovirus vaccine (OPV): _____ vaccine
Salk, Sabin
Coxsachievirus-CVB3-Induced Myocarditis
* Myocarditis: Inflammation of the heart
muscle cells
* 20% of sudden unexpected death in young
adults
**** _______ cardiomyopathy
Myocarditis Heart
Dilated
ALL
Family: Togavirida
General properties of Togaviridae
* Morphology and structures
* Classification
* EE (EEV, WEV, and VEV)
* SAV
* Chikungunyavirus
* Pathogenesis
* Epidemiology
47
II.
Toga: from Latin toga “cloak”
an outdoor
overgarment, typically
sleeveless, that hangs
loosely from the
shoulders
Classification of Togaviridae
General criteria of family Togaviridae
__-__ kb of __VE sense, non- ________ RNA
10-12, +, segmented
Family: Togaviridae
Alphavirus structure
* Envelope: lipid bilayer derived from the host
cell plasma membrane
* Contains 2 viral glycoproteins (E1 and E2)
* The only proteins in the envelopes of
alphaviruses are the viral ________,
each anchored in the lipid at or near their C- terminus.
* On the virion surface, E__ and E__ are closely paired and together form trimers that appear as “______” in an orderly array.
glycoproteins, 1, 2, spikes
Genome structure and organization of Togaviruses
51
* __Ve ____ RNA , ___-__ kbs long
* The virion RNA: infectious and serves as both genome and viral messenger RNA
* The whole genome: translated in a ___-______ polyprotein
* Structural polyprotein: expressed through a __________ ______
* The 5’-terminus carries a ___ and the 3’-terminus has a _______ ___
* ~11.7kb, 4-8% total weight of particle
* NSP encoded at the 5’ end
+, SS, 10-12, non-structural, subgenomic mRNA, cap, PolyA tail
Replication cycle of Togaviruses
Human/animal Risks and Outcomes
Human
* Eastern equine encephalitis
– ______ most at risk
– Case fatality rate: 33%
* Western equine encephalitis
– _____ <1 year most at risk
– Case fatality rate: 3%
* Venezuelan equine encephalitis
– ______ most often affected
– Fatalities are rare
Animal Risks and Outcomes
* Case-fatality rate in horses
– EEE ~ 90%
– VEE ~ 50 to 90%
– WEE ~ <30%
* Vaccine available
in the U.S
Elderly, Children, Children
EEEV is maintained in infection cycles which involves passerine birds and ditch
mosquitoes (Culiseta melanura)
* Periodic epidemic outbreaks of EEEV in wild birds involve mosquito species such
as Aedes solicitants and Coquillettidia perturbans which feed both on birds and on
mammals.
* VEEV is maintained in sylvatic cycles involving rodents and mosquitoes (Culex
species) in swampy habitats
* The cycle of infection of WEEV involves mosquitoes, usually Culex tarsalis and
indigenous wild birds.
Equine Encephalitis
(Eestern EE, Western EE, Venezuelan EE)
EEE, WEE, VEE
Mosquito-borne viral infections cause severe
encephalitis in horses and humans
Some of these viruses also cause disease
occasionally in other mammals and birds
All of them have the same epidemiological,
pathological and control outlines
* They occur in North, Central, and South
America
* Mosquitoes and birds or rodent act as
reservoirs of each virus
*
* Viruses are primarily carried by birds or
rodents and transmitted by mosquitoes
Head pressing
Transmission cycle of EEV and VEE
Transmission and pathogenesis of equine viral encephalitis
______ & _______: considered **dead-end** hosts for EEE &WEE viruses;
-direct horse-to-horse or horse-to-human transmission does not occur
** Unlike the EEE and WEE viruses, the VEE virus: shed in the ____ and _____
secretions of infected animals,
-transmission of disease by direct contact or aerosolization
an infected equine is capable of infecting a susceptible animal or human
* Infection follows the bite of infected mosquito
*** Virus replicate at site of ____ and regional _______ _____
* Generalized infection and viremia in which the virus replicates in the
lymphoid tissues throughout the body
*** Virus entry into ____ after replication in the endothelial cells lining the blood
vessels in the brain
Horses, humans, oral, nasal, bite, lymph nodes, CNS
Do not need to know this
ALL
Clinical signs of equine viral encephalitis
* Clinical sings: CNS involvements
-sever depression, behavior change,
-animal unable to stand on feet
-central blindness, paralysis, and
-death soon after the onset of clinical sings
Equine viral encephalitis
Diagnosis of equine viral encephalitis
** Ante mortem:
* serology
– Virus neutralization
– Hemagglutination inhibition
– ELISA
– Complement fixation
– Virus isolation
** Post mortem
– Virus identified in tissues (brain)
– Immunohistochemistry, ELISA, RT-PCR
Equine Encephalitis Summary
* West Nile Encephalitis
–* Late ________ through ________
– ? signs
–* ______/________ common
–___% mortality
* Eastern Encephalitis
–* ____ through late _____
–* Brain (cerebral) signs always
– 90% mortality
* Western Encephalitis (similar to EEE; 30% mortality)
summer, December, Spinal cord/brain, Tremors, weakness, 30, Spring, summer
Salmoind Alphavirus- (SAV)
* Genus Alphavirus, family Togaviridae
* 4 structural capsid glycoproteins (E1, E2, E3, and **6K) by the 3′ end and
4 nonstructural proteins (nsP1-4) by the 5′ end
** E__ has an important function in receptor _______ to host cell
mediating the internalization of the virus, playing major role in the final
envelope formation and in the budding of new viruses
* Six subtypes of salmonid alphavirus (SAV1–6) have been reported
* Different subtype strains tested being serologically closely related
members of the same viral species
** Sleeping disease: in rainbow trout is known to be caused by the ______
subtype of SAV (SAV__)
** SAV2 has been divided into two subgroups named ________ variant
(SAV2 FW) and ______ variant (SAV2 MW)
* SAV2 MW: responsible for pancreas disease (PD) in seawater-reared
Atlantic salmon
** SAV3: has been isolated from _______ Atlantic salmon in Norway hence
it is also named ________ _____ alphavirus (NSAV). It causes __________ disease in Atlantic salmon and sea-reared
rainbow trout
** SAV3: has genomic organization identical to that of SAV__ and SAV____
* SAV3 has only been detected in Norway, where until 2010 no other
subtypes were detected
* Subtypes 4–6 of SAV (SAV4–6) have been detected in Scotland and
Ireland in connection with PD outbreaks
2, binding, second, 2, freshwater, marine, farmed, Norwegian salmonid, pancreas, 1, 2
A- Young rainbow trout signs of Sleeping
diseases (SD), including failure to
keep position in water, distended
abdomen, bilateral exophthalmia
B- Skeletal muscle lesions during acute
infection
C- Skeletal muscle lesions during chronic
infection
D- Partially purified and then negative
staining EM of SAV
Commercial vaccines against SAV
Box around type and delivery method
norvax compact PD is highlighted
Chikungunyavirus-CV
** CV: ___RNA virus belongs to _______, genus _______
* Chikungunya derives from a word in the Kimakonde/Makonde language,
meaning “to become _________”, and describes the stooped appearance of
sufferers with joint pain (arthralgia).
** CV: transmitted to humans via the bite of an infected __________
** Aedes spp., Aedes ______ and Ae. _______
**** Nonhuman and human ______ are likely the main reservoirs of the virus, and
human-to-vector to-human transmission occurs during outbreaks
* CV: causes large outbreaks with high attack rates, affecting one-third to three-
quarters of the population in areas where the virus is circulating
** CV: infection causes sudden onset of high _____ ____ pains
* Headache, myalgia, arthritis, conjunctivitis, nausea, vomiting, or a
maculopapular rash
* No specific antiviral treatment is available for chikungunya
ss, Togaviridae, Alphavirus, contorted, mosquito, aegypti, Albopictus,, primates, fever, joint
Study all boxed + chikungunya
Vaccine against SAV
skipped
III: Family: Arenaviridae
** The first Arenavirus, _________ _______
virus (LCMV), was isolated in 1933
** LCMV was found to be a cause of aseptic (nonbacterial) ________
Lymphocytic choriomeningitis, meningitis
study
General properties of Arenavirus
* Virion: are pleomorphic, enveloped, -300
nm in size
* Virion contains non-functional host-cell
riboisomes
** Virions contains at least two _______ _______ nuclocapsid with associated ____-dependant RNA polymerase
* **Genome: consists ____ segments,
large 7.2, small 3.4 kb of SS RNA both _______
** Replication occur in the ________:
generally noncytocydal; persistent
infection
*** ________ from the plasma membrane
** Genetic re-assortment occur between closely related viruses.
circular, helical, RNA, two, Ambisense, cytoplasm, Budding
Arenavirus
Genome structure and organization of Arenavirus
Replication cycle of Arenavirus
Arenaviruses
* Arenaviruses are divided into
two groups – New World and
Old World viruses based on
genetic differences as well as
geographical distribution
** New World viruses are found in
the _______ Hemisphere North
and South America
*** Ex: ______ virus
*** Old World viruses occur in the ______ Hemisphere, Africa,
Europe, and Asia
** Ex: _____ fever (LASV)
Western, Chapare, Eastern, Lassa
Classification and distribution of Arenaviruses
look at highlights
Transmission of Arenaviruses- Reservoirs & Vectors
study
Transmission of Arenaviruses (LASV)
* The rodent hosts of
Arenavirus species are
chronically infected with
virus
* Some Arenavirus types
appear to be passed from
mother rodents to their
offspring during
pregnancy
* Remain in the rodent
population generation
after generation
* Most infections are
transmitted among adult
rodents, likely via fighting
and inflicting bites.
78
LASV transmission and mortality rates in humans
Comparison of the disease phenotypes between OW and NW Arenaviruses
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