Order: Mononegavirales & Family: Paramyxoviridae Flashcards
Where does the name Mononegavirales come from?
mono = single
nega = RNA genome
What 4 families are members of Mononegavirales?
- Paramyxoviridae - parainfluenza, canine distemper, Newcastle disease virus, Hendra, Nipha virus, Rinderpest, measles, mumps
- Filoviridae - ebola
- Rhabdoviridae - vesicular stomatitis virus, rabies virus
- Pneumoviridae - respiratory syncytial virus
Distinguishing characteristics of Mononegavirales families:
Are Paramyxoviruses enveloped? What is their genome like? Where do they replicate?
yes - covered with large spikes
single molecule of helical negative-sense ssRNA with 7-8 ORFs coding for 10-12 proteins (NP, P, M, F, L, HN, H, G)
cytoplasm with budding from plasma membrane
What 2 things are characteristically found in host cells infected by Paramyxovirus?
- syncytium formation
- intracytoplasmic/intranuclear inclusion bodies
Paramyxoviridae vs. Pneumoviridae:
Paramyxoviridae replication:
negative sense (3’ to 5’) to positive sense (5’ to 3’)
Paramyxovirius replication cycle:
negative sense!
What proteins are responsible for attachment, fusion, nucleoprotein formation, transcriptase formation, and matrix protein formation in Paramyxoviridae and Pneumoviridae? What extra proteins does Pneumoviridae have?
- ATTACHMENT (hemagglutinin, induction of immunity): H, G
- FUSION (penetration, spread, induction of immunity): F, F
- NP (protection of genome RNA): N, N
- TRANSCRIPTASE (RNA transcription): L and P/C/V, L and P
- MATRIX (stability): M, M
(both lack neuraminidase)
SH, M2
How do Orthomyxoviruses and Paramyxoviruses compare with respect to viruses, genome, presence of RNA polymerase, capsid structure, envelop presence, size, surface spikes, and giant cell formation?
What are 3 conserved biological properties of Paramyxoviridae?
- CELL FUSION: giant cell formation
- PERSISTENT INFECTION: noncytocidal infection
- ANTIGENIC PROPERTIES: related antigens in measles, canine distemper, rinderpest, mumps, parainfluenza, and NDV
How are Paramyxoviruses able to spread throughout host cells?
budding viruses from infected cell cause viral-infected cells to produce viral fusion proteins (F, NH), causing uninfected cells to bind to and fuse with the infected cell
- SYNCYTIA FORMATION
What animals are affected by Newcastle Disease Virus (NDV)? What may act as carriers? What are 6 common results of infection?
- chickens, turkeys, domestic/wild birds (+ humans)
- sea birds, waterfowl, psittacines (pass in feces)
- greenish-dark, watery diarrhea**
- respiratory and neurological signs
- edema of the head, especially around eyes
- drop in egg production
- death within 24-48 hours, and continuing for 7-10 days
What makes Newcastle Disease Virus (NDV) and Paramyxoviruses especially virulent?
differential HN and F cleavage makes virus polyphasic/polybasic
What are the 3 pathotypes/strains of Newcastle disease virus (NDV) in the US?
- LENTOGENIC - mild pathogenicity (Hitchner B-1, F, LaSota); used for vaccine purposes
- MESOGENIC - moderate pathogenicity (Komarov)
- VELOGENIC - severe pathogenicity (Herts, GB Texas, Melano)
What are the 3 major economic impacts of Newcastle Disease Virus (NDV)?
- high mortality
- decrease in body weight gain
- decrease in egg production
- virulent strains are reportable and can result in trade restrictions
What are the 3 tropisms of Newcastle Disease Virus (NDV)?
- respiratory tract
- GI tract
- nervous system
What are the 5 forms of Newcastle Disease Virus based on their virulence/tropism?
- DOYLE’S FORM: acute lethal infection of all ages; hemorrhages of the digestive tract (very virulent)
- BEACHE’S FORM: acute lethal infection of all ages; respiratory and neurological signs
- BEAUDETT’S FORM: mesogenic, less pathogenic form; death in young birds when used in a vaccine
- HITCHNER’S FORM: lentogenic form; mild respiratory signs (used as a live vaccine)
- ASYMPTOMATIC ENTERIC NDV: enteric form in chiefly gut infection with lentogenic virus
In what 4 ways can Newcastle Disease Virus (NDV) virulence be assessed?
- mean death time (MDT) in chicken egg embryos
- intracerebral pathogenicity index (ICPI) in day-old chicks
- intravenous pathogenicity index (IVPI) in 6-week-old chicks
- intracloacal pathogenicity test in 6-to-8-week-old chicks
What 5 factors affect the severity of Newcastle Disease Virus infection?
- virulence of the virus
- doses and age - some strains require higher doses to infect the host; young are most susceptible
- general health of the birds - stress (malnutrition, parasitism, dampness, environment) = severe long-term course
- immune status of birds - presence of lack of antibodies (vaccination)
- species of birds - chickens > waterfowl/psittacines
Newcastle disease virus (NDV) replication cycle:
How does Newcastle disease virus (NDV) use F and HN proteins to fuse with host cell membranes?
- F trimer is present on the viral membrane surface deactivated, while HN has its 4 heads down
- HN turns its 4 heads up and binds to the host cell sialic acid receptors
- upon receptor binding, F trimer binds to HN
- F is now activated and transforms into the HRA and HRB pre-hairpin intermediate
- refolding of the HRB linker forms a gap and fuses both membranes together
Where does the initial replication of Newcastle disease virus (NDV) occur in the host? What 3 things happen next?
mucosa of the upper respiratory tract
- primary viremia disseminates the virus throughout the body and parenchymal organs
- secondary viremia leads to CNS infection
- 100% morbidity with 90% mortality
What 2 things tend to result in species that show few/no signs of infection with Newcastle disease virus (NDV)?
- carrier state
- cyanosis and edema in ornamental outgrowths (combs and wattles) due to URT mucosa replication
What 3 postmortem lesions are expected in Newcastle disease virus (NDV) infection?
- hemorrhagic internal organs, like tracheal mucosa, proventriculus, and intestinal mucosa - characteristic pinpoint lesions between proventriculus and gizzard
- edema of head and neck
- edema, hemorrhage, necrosis, or ulceration of lymphoid tissue
What are the 8 most common clinical features of Newcastle disease virus (NDV) infection?
- torticollis
- abundant oral secretions
- greenish fecal material
- severe dyspnea and gasping
- hemorrhagic proventricular papillae
- hemorrhagic trachea
- cecal tonsil necrosis
- soft-shelled, roughened, deformed eggs
What is commonly seen in the brain with velogenic/viscerotropic Newcastle disease virus (NDV) infection?
perivascular cuffing (inflammation around blood vessels)
Clinical and pathological features of velogenic viscerotropic Newcastle disease virus (NDV):
A = hemorrhage in lymphoid patch in the lower eyelid (characteristic early feature)
B = focal hemorrhage and necrosis of cecal tonsils
C = hemorrhagic foci in proventriculus
D = mottled spleen with multifocal necrosis
E = paresis
F = brain lesion (gliosis)
G = virual nucleocapsid protein in spleen
H = viral RNA in cecal tonsils
What is exotic Newcastle disease virus (NDV)? What is a hypothesis to its introduction into the US? What is the most common lesion found upon infection?
viscerotropic velogenic strain (VVNDV) causing reportable disease, but not reported in the US
smuggling backyard and gamefowl —> 2002-2003 outbreak in CA, NV, AZ, TX, Mexico
hemorrhagic, ulcerative, and necrotizing lesions in the GI tract epithelium and associated lymphoid tissues
What samples from live/dead birds can be taken for Newcastle disease virus (NDV) diagnosis? What 3 lab tests are commonly done?
LIVE = tracheal, cloacal, and fecal swabs, sera
DEAD = tissues from lungs, kidneys, intestines, spleen, brain, liver, and heart
- serology: hemagglutination inhibition test, ELISA, PCR, sequencing
- pathogenicity assessments: plaque test in chicken embryo fibroblast cultures, mean death time, intracerebral pathogenicity index, intravenous pathogenicity index
- detection of viral nucleic acids by rtPCR
How is Newcastle disease virus (NDV) inoculated? What lesions are seen in embryos?
- into 10-12 days old hen embryonated eggs via CAM or allantoic sac
- grows well on chicken embryo fibroblast cell culture
hemorrhagic lesions with encephalitis and embryo death within 34-72 days
When are Newcastle disease virus (NDV) vaccines given? What is a major drawback?
2-4 weeks of age or at 1 day of age via conjunctiva
- live
- inactivated
- newplex: virus antibody complex
- lentogenic strains (LaSota live attenuated): eye drops, water, spray
- during outbreaks = mesogenic strain IM + booster 3-4 weeks later
vaccine-induced immunity is short-lived = 8-10 weeks due to strain variation in virulence
What is the best way to prevent and control Newcastle disease virus (NDV) infection?
GOOD BIOSECURITY
- avoid contact with feral birds of unknown health status
- quarantine and isolation of newly purchased birds for ~30 days
- transport birds in new/disinfected containers
- restrict personnel movement between new and old birds
- disinfecting
- disposal of destroyed birds, contaminated products, insects, and mice
- controlled handling of bird carcasses, liter, and manure
no known treatment
What is the most common presentation of Newcastle disease in humans? What is not affected? Is there human-to-human spread?
eye infections
- reddening
- excessive tearing
- eyelid edema
- conjunctivitis
- subconjunctival hemorrhage
cornea
NO
Cytopathic effect in Vero cells infected with avian paramyxoviruses (APMVs):
What causes Rinderpest (cattle plaque)?
Rinderpest virus (RPV)
- order: Mononegavirales
- family: Paramyxoviridae
- genus: Morbilivirus
What is Rinderpest? In what 3 ways is it transmitted?
acute, highly contagious viral disease of cattle, domesticated buffalo, and most cloven-footed wild animals
- direct contact with nasal/ocular secretions, feces, urine, saliva, and blood
- ingestion of contaminated food or water
- close indirect contact with infected animal fomites
What are the 2 most infectious periods of Rinderpest infection? Is there a chronic carrier state? Does wildlife act as a reservoir?
1-2 days before clinical signs and 8-9 days after onset of clinical signs
no, no
What are the 6 clinical signs of classical Rinderpest?
(acute form)
1. fever, depression, anorexia
2. constipation followed by hemorrhagic diarrhea
3. serous to mucopurulent nasal/ocular discharge
4. necrosis and erosion of the oral mucosal
5. enlarged lymph nodes
6. congestion and hemorrhage of the rectum (zebra stripe)
How is Rinderpest infection diagnosed? How can infection be controlled?
isolation of the virus in a proper cell line wth confirmation by antigen/nucleic acid detection with agar-gel precipitin test, ELISA, IP, IF, and rtPCR
- destroyed by phenol, cresol, sodium hydroxide, and lipid solvents
- quarantines
- movement controls
- vaccination: cell culture adapted
(has been eradicated from most regions of the world)
What causes goat plague?
Peste des Petits Ruminants virus (PPRV) - ovine rinderpest
- order: Mononegavirales
- family: Paramyxoviridae
- genus: Morbilivirus
What is goat plague? What are 5 clinical signs?
acute/subacute viral disease of goats and sheep
1. fever
2. erosive stomatitis
3. conjunctivitis
4. gastroenteritis
5. pneumonia
What is Peste des Petits Ruminants virus (PPRV) antigenically similar to? Where is infection most common?
rinderpest virus
African countries, Middle East, India
What 2 things are required for transmission of Peste des Petits Ruminants virus (PPRV)? Is it able to infect humans?
- close contact with ocular, nasal, and oral secretions and feces
- inhalation of aerosols from sneezin and coughing animals
no
How is Peste des Petits Ruminants virus (PPRV) infection prevented? How long does a tissue culture rinderpest vaccine last?
- destroyed by most common disinfectants, like phenols, sodium hydroxide, ether, and detergents
- quarantine
- culling
- burning/burying carcasses
- import restrictions
- vaccine in African countries
12 months
What causes canine distemper?
canine distemper virus (CDV)
- order: Mononegavirales
- family: Paramyxoviridae
- genus: Morbilivirus
What systems does canine distemper virus (CDV) attack? What animals do they infect? What is the main route of infection?
respiratory, GI, and nervous systems
wild carnivores, like foxes and wolves
inhalation of aerosol droplet secretions from infected animals
What are 10 clinical features of canine distemper?
- eye and nose discharge
- depression, loss of appetite (anorexia)
- biphasic fever
- conjunctivitis
- diarrhea, vomiting
- pneumonia, rhinitis
- acute encephalomyelitis + neurological disease
- hyperkeratosis of footpad (hardpad) and nose
- loss of tooth enamel
- pustular dermatitis (acne)
What is characteristically found in host cells infected with canine distemper virus?
intracytoplasmic inclusion bodies
What are the 5 steps to the pathogenesis of canine distemper virus (CDV)?
- CDV infection via aerosols and colonization in lymphoid tissues
- primary CDV replication in the lymphoid tissues (tonsils)
- CDV infects macrophages in lymphatic ducts
- CDV enters the CNS via cerebral circulation, choroid plexus, and CSF
- infection via olfactory nerve by pyriform lobes of the brain
CDV pathogenesis:
What clinical specimens can be taken from live and dead animals for canine distemper diagnosis? How is the diagnosis confirmed?
LIVE: tonsil or conjunctival swabs, sera
DEAD: lungs, lymph nodes, intestine, kidneys, thymus, spleen
- virus isolation
- seroconversion using paired serum samples: ELISA
- histologic lesions: intracytoplasmic inclusion bodies in stained blood, neutrophils, or eye smears
- clinical signs
How is canine distemper diagnosed in the clinic?
SNAP test - Standard Network Access Protocol
What is the best way to prevent canine distemper? What can be used prophylactically? How are antibiotics used in distemper cases?
vaccination at 8 weeks, then 12-16 weeks, then 1x/yr
- canine tissue culture adapted
- chick embryo adapted
- live attenuated
IgG
treats secondary infections due to immune suppression
What virus causes Shipping Fever? How is it transmitted?
bovine parainfluenza type-3 virus (PI-3)
- order: Mononegavirales
- family: Paramyxoviridae
- genus: Respirovirus
aerosol inhalations
What cells are targeted by bovine parainfluenza type-3 virus (PI-3)? What are 5 common signs?
epithelial cells of the respiratory tract (alveolar cells)
(Shipping fever)
1. high fever
2. conjunctivitis
3. respiratory distress
4. mucopurulent rhinitis
5. fibrinous pneumonia
What vaccine is used against multimicrobial Shipping fever?
(bovine parainfluenza type-3 virus (PI-3))
pentavalent vaccine - IBR, BRSV, PI-3, BVD killed vaccine + Haemophilus somnus/Pasteurella haemolytica bacterins
What virus causes kennel cough? What is kennel cough?
canine parainfluenze virus type-2 (PI-2)
- order: Mononegavirales
- family: Paramyxoviridae
- genus: Respirovirus
infectious tracheobronchitis (localized in URT) with sudden onset of mild fever, nasal discharge, and a harsh non-productive cough
What are the 2 microbes most commonly causing kennel cough? What vaccine is used against it?
- Bordetella bronchiseptica (80%)
- canine parainfluenza virus type-2 (20%)
canine parainfluenza + canine adenovirus-2
What virus causes blue eye disease in pigs? In what pigs is it most common?
porcine rubulavirus (PoRV), a Paramyxoviridae
nursing or growing pigs with CNS signs
What specimen can porcine rubulavirus (PoRV) be found in? How is it transmitted?
nasal secretions, urine, semen
direct nose-to-nose contact
What is the pathogenesis of porcine rubulavirus (PoRV)?
blue eye disease
- PoRV binds sialic acid-expressing cells and replicated in the nasal mucosa and tonsil
- spreads to the brain via cranial nerves proximal to the oral cavity and to other organs via blood
What are the 3 symptoms of blue eye disease in pigs? Etiology? Where can these cells be isolated from?
- conjunctivitis with adherence of the eyelids
- corneal opacity (blue eye) in one or both eyes
- encephalomyelitis in youngs and growing pigs
porcine rubulavirus (PoRV)
from the brain or tonsil in PK-15 cells
What is the Sendai virus? Where was it first observed? What does it naturally infect?
murine parainfluenza virus-1
when human lung material was inoculated in lab mice
mice, rats, and hamsters where it is highly contagious
- limited disease in pigs!
What are 6 clinical signs of Sendai virus infection? How
- roughened hair coat
- eye crusting
- dyspnea
- mortality in adults
- weight loss
- fetal resorption
How does Sendai virus infection affect those that survive?
- immunocompetent will not have persistent infection or carrier status
- antibodies persist for life
Where is Atlantic salmon paramyxovirus infection observed? What are 2 clinical signs?
Norway - significant losses in aquaculture industry
- proliferative gill inflammation
- gill pallor
What does bovine respiratory syncytial virus (BRSV) most commonly cause? What are 6 clinical signs?
(order: Mononegavirales; family: Pneumoviridae; genus: Pneumovirus)
acute pneumonia in calves
1. coughing, dyspnea, polypnea
2. fever
3. anorexia
4. nasal discharge
5. pneumonia with bronchitis and alveolitis with multinucleated syncytia
What acts as a reservoir for bovine respiratory syncytial virus (BRSV)? How is it shed? How is it controlled?
infected animals shedding in nasal secretions
vaccination after maternal antibody decline
What are 4 common postmortem lesions seen in lungs infected with bovine respiratory syncytial virus (BRSV)?
- consolidation
- emphysema
- pneumomediastinum
- voluminous and heavy - fail to collapse
How is bovine respiratory syncytial virus (BRSV) infection diagnosed?
- virus isolation and detection
- rtPCR
- seroconverstion
- ELISA
- histopathology: bronchiolitis and syncytia formation
What is natural immunity to bovine respiratory syncytial virus (BRSV) like? How is infection controlled?
short-lived, reinfection common - maternal antibodies do not protect against reinfection, but can reduce severity
(HARD - ubiquitous, persistent)
- decrease movement of cattle between herds
- modified live vaccine
- (parenteral) inactivated vaccine: less effective
- maternally derived antibodies
What does avian metapneumovirus (AMPV) cause? What are 5 clinical signs?
turkey rhinotracheitis (TRT) + chickens and ducks
1. swollen head syndrome in broilers and broiler breeders
2. significant drop in egg production in chickens and ducks
3. serous ocular and nasal discharge
4. frothy eyes
5. conjunctivitis
What are the subtypes of avian metapneumovirus (AMPV)? Which are the most similar?
subtypes A to D
- European subtypes A, B, and D
What is necessary for diagnosis and isolation of avian metapneumovirus (AMPV)?
DIAGNOSIS: viral detection and serology (rtPCR targeting F, N, or G genes; commercial ELISA kits)
ISOLATION: inoculation of 6-8 day old embryonated chicken or turkey eggs via the yolk sac route
What was Hendra virus formerly called? What does it cause? What is its reservoir? What animals are not infected?
Equine morbillivirus
high mortality in horses and humans with frothy nasal discharge
fruit bats (flying foxes)
dogs, rats, mice, chickens
Hendra virus transmission:
What is Nipah virus? What does it cause? What acts as a reservoir?
- order: Mononegavirales
- family: Paramyxoviridae
- genus: Henipavirus
respiratory and neurological (fatal encephalitis) diseases in pigs and humans (BSL4 agent, ZOONOTIC)
fruit bats (flying foxes)
How is Nipah virus infection diagnosed?
- rtPCR from body fluids
- ELISA to detect viral antibodies
- virus isolation
What are the 5 Morbiliviruses that affect marine mammals? What are they collectively referred to as?
- canine distemper virus (CDV)
- phocine distemper virus (PDV) in seals and sea otters
- dolphin morbillivirus (DMV)
- pilot whale morbillivirus (PWMV)
- Longman’s beaked whale morbillivirus (LBWMV)
acetan morbillivirus (CMV) in porpoise, dolphin, and whales
What is measles virus?
highly contagious virus first described in the 7th century causing illness and near-universal childhood infection in the pre-vaccination era
- common and often fatal in developing areas
