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MB4030 > L7: Influenza Virus > Flashcards

L7: Influenza Virus Flashcards

1
Q

How many subtypes of Influenza virus are there, and which is the most virulent?

A

3 subtypes: A, B & C
Influenza A is the most virulent

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2
Q

Viral surface antigens on Influenza?

A

Haemagglutinin and Neuraminidase

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3
Q

Main reservoir of Influenza virus

A

aquatic birds

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4
Q

What gives rise to Influenza virus epidemics and pandemics?

A

genetic variation

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5
Q

What is antigenic shift?

A

Gene swapping in cells simultaneously co-infected with two different Influenza viruses
- unpredictable, leads to the formation of new strains

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6
Q

Antigenic shift only occurs in which subtype of Influenza?

A

A

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7
Q

What is antigenic drift?

A

Point mutations leading to small change to ‘protein coat’
- causes seasonal variation

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8
Q

Antigenic drift occurs in which subtypes of Influenza?

A

Both A and B

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9
Q

New strains of Avian Influenza

A

H5N1 and H7N9

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10
Q

Reproductive number of seasonal flu

A

~1.3

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11
Q

Influenza virus rapidly infects which cells?

A

epithelial cells of the respiratory tract

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12
Q

Influenza virus RNA is recognised by __, leading to secretion of __ and __.

A

PRRs
IFNs and proinflammatory cytokines/chemokines

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13
Q

What induces an anti-viral state and how?

A

Interferons (produced by macrophages and pDCs) by stimulating the expression of 100s of ISGs

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14
Q

What effect do chemokines have in Influenza virus infection?

A

They recruit neutrophils, monocytes and NK cells to airways. This results in neutralising antibodies on mucosal surfaces and in serum to prevent re-infections. CD4 & CD8 T cell responses and memory develop.

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15
Q

TLR7 signalling induces…

A

NF-κβ-dependent genes from the NF-κβ endosome, and IRF7 activation from the IRF7 endosome.

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16
Q

Matrix 2 ion channel activity in the Golgi stimulates…

A

formation of the NLRP3 inflammasome, which results in caspase 1 activation and the release of cytokines IL-1β & IL-18

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17
Q

Influenza proteins that interfere with PRR signalling and IFN production

A
  1. NSI (highly expressed in cytoplasm and nucleus): competes with RIG-1 for binding dsRNA
    - Blocks expression of ISGs
  2. PB1-F2: destabilises MAVS complex
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18
Q

URT is mostly protected from Influenza virus by…

A

secretory IgA1, whereas IgG1 is dominant in the LRT

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19
Q

Haemagglutinin needs to be __ to produce infectious virus particles.

A

cleaved into H1 and H2 subunits
(this typically happens once the virus is released from the cell and is mediated by airway proteases)

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20
Q

Antibodies to the H stalk, N, and M2 proteins can trigger…

A

Fc receptor-mediated effector functions against infected cells, such as ADCC

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21
Q

Antibodies to the H stalk have also been shown to activate __.

A

complement

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22
Q

Clearance of virus-infected cells is by __.

A

CD8+ T cells

23
Q

The most immuno-dominant viral proteins for T cells responses are __ and __.

A

nucleoprotein and matrix protein

24
Q

Humoral vs cell-mediated immunity to Influenza virus

A

Humoral: comprises B cells, which after interaction with Influenza differentiate into Ab-secreting plasma cells

Cellular response: starts with Ag presentation via MHC I & II molecules by DCs, which then leads to activation, proliferation & differentiation of antigen-specific T cells (CD4 or CD8). These cells gain effector cell function to either help directly (release cytokines) or mediate cytotoxicity following recognition of Ag.

25
Q

Another name for bird flu

A

Highly Pathogenic Avian Influenza Virus (HPAIV)

26
Q

What strains of Avian Influenza are found in humans?

A

H5N1, H7N3, H7N7, H7N9

27
Q

What strain is responsible for seasonal flu?

A

H1N1/H3N2

28
Q

Seasonal flu vs bird flu in humans

A

Seasonal flu:
- Easily spread, rarely fatal
- Strong tropism for URT
- Virus attaches to ciliated epithelial cells, causing necrosis of respiratory epithelium & infiltration of LP by lymphocytes
- Leads to rhinitis, paranasal sinusitis, pharyngitis, laryngitis

HPAIV H5N1:
- Spreads slowly, often fatal
- Strong tropism for LRT
- Binds to: Clara cells lining bronchioles, alveolar macrophages, Type II pneumocytes lining alveoli
- Alveolar damage & flooding of alveolar lumina by oedema fluid

29
Q

What strain is primarily responsible for bird flu in humans?

A

HPAIV H5N1

30
Q

Clinical findings of H5N1/H7N9 infection

A
  • Severe illness complicated by ARDS & multiorgan failure
  • ~90% present with pneumonia & lymphopenia
  • Large scale production of inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα) and chemokines (CCL2/MCP-1, IP-10)
31
Q

Inflammatory cytokines associated with H5N1/H7N9 infection

A

IL-1β, IL-6, IL-8, TNF-α
Chemokines: CCL2/MCP-1, IP-10

32
Q

What does IL-8 attract to the lung?

A

neutrophils

33
Q

What effect do some mutations of NS1 gene in H5N1 have?

A

They make NS1 an even more potent inhibitor of IFN production

34
Q

What is the likely reason for the severity of HPAIV H5N1 infection?

A

A combination of high replication in alveolar macrophages and induction of secreted pro-inflammatory cytokines by infiltrating macrophages

35
Q

Human Influenza virus binds preferentially to?

A

sialic acid-alpha 2,6 galactose receptors

36
Q

Avian Influenza virus (H5 and H7) binds preferentially to?

A

sialic acid-alpha 2,3 galactose receptors (mainly in GIT)

37
Q

‘Events’ that need to occur for H5N1-like viruses to successfully infect humans

A
  1. Optimal temp of replication would need to shift from 40℃ to 37℃
  2. Site of replication from intestinal to respiratory tract
  3. Virus receptor specificity changing from α2,3 sialic acid to α2,6 sialic acid
    - Intermediate hosts, like swine and domesticated poultry could play a role (they possess both sialic acid receptors)
38
Q

Which strains of Avian Influenza are highly pathogenic in humans & domesticated poultry, and are less pathogenic in aquatic bird reservoirs?

A

H5 and H7 strains

39
Q

Recommended quadrivalent formulation of egg-based Influenza vaccines for 2022-2023 Influenza season contain the following:

A
  1. an Influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus;
  2. an Influenza A/Darwin/9/2021 (H3N2)-like virus;
  3. an Influenza B/Australia/1359417/2021-like virus (B/Victoria lineage); and
  4. an Influenza B/Phuket/3073/2013-like virus (B/Yamagata lineage).
40
Q

The insufficient effectiveness of seasonal Flu vaccines are sometimes blamed on…

A

an antigenic mismatch between the vaccine strain of the virus and what is actually in circulating at the time.

41
Q

Original Antigenic Sin Theory

A

holds that Flu epitopes encountered in early childhood permanently shape the antibody response to subsequent exposure to Flu strains, and are dominated by antibodies that were made to conserved epitopes from the 1st early childhood exposure

42
Q

Flu Vaccine is traditionally made by

A

inoculation of selected strains of Influenza virus (both A & B) into embryonated chicken eggs, virus is then inactivated prior to vaccination

43
Q

Quadrivalent vaccines, which protect against a second lineage of B viruses, are recommended to contain:

A

B/Phuket/3073/2013-like (Yamagata lineage) virus

44
Q

FluMist is an example of

A

a live, attenuated Influenza vaccine

45
Q

FluBok Quadrivalent

A

Contains 4 full-length recombinant HA proteins against: 2 A strains (H1N1 and H3N2) & 2 B strains

46
Q

4 criteria for a universal flu vaccine

A
  1. 75% effectiveness against symptomatic Influenza infection
  2. Protection against both Group 1 and Group 2 Influenza viruses
  3. Durable protection that lasts at least 1 year
  4. Be suitable for all age groups
47
Q

2 domains of Haemagglutinin

A
  1. a HEAD composed of a sialic acid, containing the glycoprotein receptor that mediates attachment to host cells
  2. STEM domain, located proximal to the viral envelope, involved in fusion to the host cell membrane
48
Q

Most neutralising antibodies to H are to

A

the ‘exposed’ head region and they block virus attachment to cells

49
Q

What allows Influenza viruses to escape the antibody response?

A

Antigenic drift changes

50
Q

For seasonal Influenza infections/vaccination, the predominant MBC response is to __.

A

the HA head

51
Q

Stem-directed antibodies are __ prevalent in serum and are __ potent than those directed at the head.

A

less prevalent
less potent

52
Q

Are HA head or steam antigens more accessible to the immune system?

A

head

53
Q

Which neutralising antibodies cross-react with most group 1 Influenza A HA subtype viruses?

A

CR6261 and F10 (both bind to a hydrophobic pocket on the STEM)

MB4030 (10 decks)

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