Family: Orthomyxoviridae Flashcards

1
Q

Where does the name Orthomyxoviridae come from?

A

ortho = direct
myxo = mucous

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2
Q

What is the structure of Orthomyxoviridae virions?

A

enveloped, usually rounded but can be filamentous

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3
Q

What is the genome of Orthomyxoviridae like?

A

linear, segmented (8) negative-sense ssRNA encapsidated by nucleoproteins
- each segment forms a ribonucleoprotein complex

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4
Q

What are the 3 types of influenzaviruses in Orthomyxoviridae? Which one is unique?

A

A, B, C

only influenza A viruses are classified by subtype main surface glycoproteins - hemagglutinin (HA), neuraminidase (NA, H1N1)

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5
Q

What types of influenza can humans be infected with? Which 3 are of the highest importance? Animals?

A

HUMANS: A, B, C
- A: H1N1, H1N2, H3N2
ANIMALS: A, (D in cattle)

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6
Q

What is the purpose of hemagglutinins and neuraminidases in influenza viruses? How many of each are there?

A
  • H = attachment, 16 distinct ones
  • N = drill, host cell entry, 9 distinct ones
  • host immune response is directed at these proteins
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7
Q

What is the natural host of all known subtypes of influenza A viruses? How does it affect them? How does it affect other animals?

A

wild birds - do not become sick

domestic poultry (turkeys, chickens) can become sick and die

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8
Q

What are the 5 important genera in Orthomyxoviridae?

A
  1. influenza A
  2. influenza B
  3. influenza C
  4. Thogotovirus
  5. Isavirus
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9
Q

How are influenza viruses classified?

A
  • type (A/B/C)
  • place isolated
  • number of isolate
  • year isolated
    (and, in influenza A, HA (H) and NA (N) subtypes)

EX: A/Solomon Island/3/2006 (H1N1)
EX: B/Malaysia/2506/2004

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10
Q

Host range of influenza A, B, C, and D viruses:

A

pathogenesis and transmission in humans and pigs

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11
Q

What is the purpose of the proteins encoded in the 8 segments of influenzavirus’ genome?

A
  1. = PB2 = RNA transcriptase
  2. = PB1 = RNA transcriptase
  3. = PA = RNA transcriptase
  4. = HA = hemagglutinin envelop trimer for attachment
  5. = NP = RNA and polymerase proteins
  6. = NA = neuraminidase envelop tetramer
  7. = M1/M2 = matrix protein, membrane protein for uncoating
  8. = NS1/NS2 = nonstructural, inhibits pre-mRNA splicing
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12
Q

Distribution of hemagglutinins between birds and mammals:

A

2009-2010 - H1N1 swine flu

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13
Q

How is the hemagglutinin (HA) processed and matured within the host?

A

it is cleaved by epithelial cells of the respiratory and digestive tract

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14
Q

How do the influenzavirus surface antigens compare?

A

HEMAGGLUTININ:
- trimer of lollipops structure with fibrous stem anchored into the membrane
- binds to host cells receptors (sialic acid)
- main target of neutralizing antibodies

NEURAMINIDASE:
- box-shaped tetramer with a stalk anchored into the membrane
- cleaves neuraminic acid to release viral progeny from infected cells
- degrades protective layers of mucin in the respiratory tract
- plays minimal role immunity to influenza

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15
Q

Where does influenza virus bind within the host? How does it enter cells? How does it leave?

A

binds onto sugars (sialic acid) on the surfaces of epithelial cells in the nose, throat, and lungs of mammals and intestines of birds

internalized into endosomes
budding

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16
Q

What parts of the host cell sialic acid receptors does influenza attach to?

A

HUMANS = α2,6
AVIAN = α2,3

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17
Q

What are the main 2 differences between Orthomyxovridae and Paramyxoviridae?

A

ORTHO = ssRNA negative-sense genome segmented into 8 pieces, replicates in the nucleus

PARA = single molecule of ssRNA negative-sense genome, replicates in the cytoplasm

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18
Q

What are the 5 most common symptoms of seasonal influenza in humans?

A
  1. chills
  2. body aches, especially in throat and joints
  3. coughing and sneezing
  4. extreme fever with fatigue and headaches
  5. nasal congestion
    - similar symptoms to colds, but much more severe
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19
Q

In what 2 ways is influenza transmitted?

A
  1. inhalation of aerosol droplets/droplet nuclei
  2. direct/indirect contact with infected individual
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20
Q

How does antigenic shift and antigenic drift affect influenza progeny?

A

ANTIGENIC SHIFT = two influenza viruses enter host cell and intermix RNA, resulting in subtypes

ANTIGENIC DRIFT = accumulation of mutations over time in one virus results in the production of progeny with small mutations

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21
Q

What is influenza reassortment?

A

pigs co-infected with avian (H5N1) and human (H3N2) influenza viruses result in reassortment (shift) of RNA and the production of a hybrid new subtype
- only occurs in influenza A viruses
- pig = smoothie mixer, species jump

22
Q

What are the 3 most common strains of swine influenza virus? Which 2 are endemic in pig populations?

A
  1. H1N1*
  2. H1N2
  3. H3N2*
23
Q

Where does human influenza A viruses start?

A

avian influenza

24
Q

What are the reservoir and spill-over hosts of influenza virus?

A

RESERVOIR = chickens (esp backyard flocks in contact with migratory wild birds), duck, geese, terrestrial poultry

SPILL-OVER = felids (including cats), humans, pigs, non-migratory wild birds, viverrids, stone marten

25
Q

What causes avian influenza? What are the 2 versions of avian influenza virus? What is the difference based on?

A

type A strains of influenza

  • LPAI = low pathogenic avian influenza; respiratory and intestinal infection (can evolve into HPAI)
  • HPAI = high pathogenic avian influenza (H5+H7); systemic infection

molecular genetics and pathogenesis criteria

26
Q

What allows new influenza strains causing pandemics to spread widely?

A

few, if any, people/animals have any immunity to the emerging strain
- new strains acquire the ability to infect people and animals and spread either by reassortment or adaptive mutations

27
Q

What is the origin of the 2009 H1N1 epidemic? Where is infection limited to?

A

H1N1 and N3H2

respiratory tract

28
Q

How does human infection range with influenza virus?

A

MILD = H7N3, H7N7
SEVERE/FATAL = H7N7, H5N1

29
Q

How does virulence compare in the 2 strains of avian influenza virus?

A
  • LPAI = mild disease in poultry associated with polutry outbreaks worldwide
  • HPAI = high mortality in domestic poultry caused by subtypes H5 and N7
30
Q

What are 10 clinical signs of high pathogenic avian influenza (HPAI) infection?

A
  1. sudden death
  2. lack on energy and appetite
  3. decreased egg production
  4. soft-shelled or misshapen eggs
  5. swelling of the head
  6. purple discoloration of the skin
  7. nasal discharge
  8. coughing, sneezing
  9. lack of coordination
  10. diarrhea
31
Q

What species are affected by equine influenza viruses? What 2 subtypes are known to circulate in equine populations?

A

horses, donkeys, mules, zebras

  1. H7N7 (equine virus 1) - extinct
  2. H3N8 (equine virus 2)**
32
Q

What are 7 signs of equine influenza in foals? Where does infection spread fastest?

A
  1. high fever
  2. deep, dry cough
  3. serous to mucopurulent nasal discharge
  4. corneal opacity
  5. enlarged submandibular LN
  6. edema of legs and scrotum
  7. enteritis

groups of animals - stables (low air circulation + close proximity)

33
Q

What is important to note about infection and developing resistance of the 2 strains of equine influenza virus?

A

infection or vaccination with H7N7 and H3N8 does not induce protections against infection with each other

34
Q

Equine influenza virus transmission cycle:

A
35
Q

Which strain of influenza is most reported in canine populations in the US? Which strain has potential to become a second canine influenza virus?

A

H3N8

H3N2 (isolated from respiratory disease ing Korea

36
Q

What are the 5 most common clinical signs of canine influenza virus infection? What can happen in acute cases?

A
  1. coughing
  2. high fever
  3. increased respiratory rate
  4. pneumonia/bronchopneumonia
  5. lethargy and anorexia

hemorrhages in respiratory tract and death

37
Q

How has equine H3N8 adapted to infect canines?

A

equine H3N8 spreads to a susceptible canine host and develops mutations (antigenic drift), creating a new subtype that is able to cause infection and spread to other canines

38
Q

What samples can be taken for influenza virus infection diagnosis? How is infection diagnosed?

A

nasal secretions or epithelial cells from a throat swab

  • detection of viral particles by EM
  • isolation on cell culture or ECE using allantoic sac inoculation after 9-11 days
  • detection of viral RNA with rtPCR
  • detection of viral antigens with HA, ELISA, FAT
  • detection of viral antibodies with ELISA, IF
  • seroconversion
39
Q

What 3 vectors are being used for equine influenza virus vaccines?

A
  1. canarypox vector
  2. modified herpes virus-1 vector
  3. modified vaccina Ankara vector
40
Q

How is the DIVA concept being used for equine influenza virus vaccines?

A
  • DIVA = recombinant canarypox virus is HA+ and nucleoprotein complex-
  • INFECTION = HA+ and NP+
  • NO DIVA = whole inactivated EIV vaccine is HA+ and NP+

NP is produced during exposure to the whole virus only and the canarypox virus lacks this, but has HA

41
Q

How can influenza virus infection be controlled?

A
  • vaccines available for pigs, horses, dogs, and birds - do not prevent infection or shedding, but causes disease to be milder due to a primed immune response
  • good hygiene
  • quarantine
  • cleaning and disinfection
  • physical barriers, like glass/plastic windows
  • PPE
42
Q

How is the influenza vaccine developed from year to year? Which viral vaccines are developed differently?

A

changes periodically to reflect current subtypes and strains in a certain geographical area

swine and equine viruses display less antigenic drift, so these vaccines are changed less often

43
Q

How do the 2 human vaccines for influenza virus compare?

A
  1. inactivated subunit - IM, trivalent, split virus/subunit types, immunity for ~1 year
  2. live attenuated - IN, trivalent, immuity lasts ~1 year, formulated annually
44
Q

What are the standard quarantine measures for HPAI?

A

INFECTED ZONE: minimum 3 km radius around infected premises
BUFFER ZONE: 3-10 km of the infected zone
CONTROL ZONE: infected + buffer zones
SURVEILLANCE ZONE: at least 10 km away from control zone

45
Q

What are the 6 recommended measures for controlling HPAI farms?

A
  1. keep poultry away from areas frequented from wild fowl
  2. keep control over access to poultry houses by people and equipment
  3. maintain sanitation of property, poultry houses, and equipment
  4. appropriate disposal of manure and dead poultry
  5. culling to eradicate disease
  6. appropriate disposal of carcasses and all of the animal by burial overlaid with limestone or incineration
46
Q

Targets for anti-influenza agents:

A
47
Q

What are the 2 classes of drugs used prophylactically for influenza infections?

A
  1. ADAMANTANES: amantadine, rimantadine
  2. NEURAMINIDASE INHIBITOR: zanamivir (Relenza), oseltamivir (Tamiflu)
48
Q

What caused the 2009 outbreak of H1N1 and H3N2 to worsen?

A

haphazard use of Tamiflu (oseltamivir) led to the production of new AMR strains

49
Q

What causes infectious salmon anemia? What salmon are most affected?

A

infectious salmon anemia virus (ISAV), a member of the family Orthomyxoviridae and genus Isavirus

farmed Atlantic salmon (Salmo salar)

50
Q

How has infectious anemia virus evolved to infect its host? What allowed for this?

A

adapted to cold-water salmonid fish and has optimum growth at 15 degrees C

nucleotide deletion in the HE gene

51
Q

How does infectious anemia present in salmon?

A
  • severe anemia and hemorrhages in several organs
  • mortality may exceed 90%
  • groups of dead fish floating