Orthomyxoviridae: Influenza Flashcards

1
Q

[8-minute video]: Influenza - Professor Dave Explains

A

🤧

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2
Q

Influenza virus
(a) Family
(b) Genera
(c) Species

A

(a) Orthomyxoviridae
(b) Alphainfluenzavirus, Betainfluenzavirus, Gammainfluenzavirus, Deltainfluenzavirus
(c) Influenza A, B, C, D viruses

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3
Q

Which Influenza serotype causes the most severe disease in man?

A

Influenza A

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4
Q

Explain how Influenza A viruses are named.

A

🛸 Influenza A viruses are named based on the combination of two surface proteins: hemagglutinin (HA) and neuraminidase (NA).
🛸 There are 18 known subtypes of HA, designated as H1 through H18.
🛸 There are 11 known subtypes of NA, designated as N1 through N11.
🛸 The specific combination of these proteins determines the subtype of the virus. For example:
H1N1: This subtype has hemagglutinin type 1 and neuraminidase type 1.
H3N2: This subtype has hemagglutinin type 3 and neuraminidase type 2.

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5
Q

Briefly discuss influenza virus structure and genome type.

A

(a) Structure
🛸 enveloped
🛸 envelope is studded with two proteins:
◾ Hemagglutinin (HA) – attachment
◾ Neuraminidase (NA) – viral release
🛸 Matrix proteins (M1 and M2) provide structural integrity and are involved in the viral life cycle.
🛸 Ribonucleoprotein (RNP) complexes: These complexes consist of viral RNA (vRNA) wrapped around nucleoproteins (NP) and associated with RNA-dependent RNA polymerase (RdRP), which is essential for viral replication.

(b) Genome
The genome of influenza viruses is composed 8 segments of negative sense, single-stranded RNA (ssRNA).

[Diagram 1] [Diagram 2] [Diagram 3]

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6
Q

What role does Hemagglutinin (HA) play in the initial step of Influenza infection?

A

HA is crucial for the initial step of viral infection as it facilitates the attachment of the virus to the host cell by binding to sialic acid residues on the surface of epithelial cells in the respiratory tract (RT).

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7
Q

Brielfy describe the hemadsorption test.

A

â—¾ The test is based on the adherence of red blood cells to the surface of virus-infected cells. Hemagglutinating viruses have surface proteins that can bind to red blood cells.
â—¾ Procedure:
(a) Virus-infected cells are cultured.
(b) Red blood cells are added to the culture.
(c) If the virus is present, the red blood cells will adhere to the infected cells, forming a visible layer.
â—¾ This test is commonly used to detect viruses like influenza, mumps and measles.

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8
Q

Discuss the role of the Neuraminidase (NA) protein in the Influenza virus life cycle.

A

NA breaks down sialic acid, preventing the newly formed viruses from sticking to the host cell surface or to each other, facilitating their release and spread.

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9
Q

Briefly discuss antigenic drift.

A

🛸 Antigenic drift occurs in all Influenza viruses.
🛸 It refers to small, gradual changes or mutations in the genes of influenza viruses. These changes occur over time as the virus replicates.
🛸 These mutations can lead to changes in the surface proteins of the virus, specifically hemagglutinin (HA) and neuraminidase (NA). These proteins are recognized by the immune system and are capable of triggering an immune response.
🛸 Because of these changes, acquired immunity may no longer be effective.
🛸 [Diagram 1] [Diagram 2]

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10
Q

Briefly discuss antigenic shift.

A

🛸 Antigenic shift is a sudden major change in an Influenza A virus, resulting in new HA and/or NA proteins. This can occur when two different influenza viruses infect the same cell and exchange genetic material.
🛸 This process can create a new Influenza A subtype with a combination of HA and NA proteins that the human population has little to no pre-existing immunity against.
🛸 [Diagram 1] [Diagram 2]

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11
Q

Discuss the transmission and pathogenesis of influenza.

A

Transmission:
🛸 Influenza viruses are primarily transmitted through small particle aerosols generated when an infected person coughs, sneezes, or talks.
🛸 These particles can be inhaled by others. Transmission can also occur via fomites, which are surfaces or objects contaminated with the virus. Touching these surfaces and then touching the face can lead to infection.

Pathogenesis:
🛸 The virus replicates in the epithelial cells lining the respiratory tract. This includes the nose, throat, and lungs.
🛸 Viremia, is rare in influenza infections.
🛸 The virus directly causes the death of infected epithelial cells.
🛸 Later in the infection, T-cytotoxic cells also contribute to cell death as they target and destroy infected cells.
🛸 The death of epithelial cells reduces the clearance of pathogens from the respiratory tract. This impaired clearance can predispose individuals to bacterial super-infections, which are secondary bacterial infections that occur following the initial viral infection.
🛸 Viral clearance is by interferon and cell-mediated immunity. Interferon is also responsible for most symptoms (fever, muscle aches).
🛸 [Diagram]

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12
Q

What are the symptoms of uncomplicated influenza?

A

🩺 Abrupt onset of symptoms
🩺 Non-specific symptoms: headache, myalgia, fever
🩺 Cough
🩺 Rhinorrhea
🩺 Rarely, vomiting and diarrhea

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13
Q

Discuss pulmonary complications of Influenza.

A

(1) Croup (Laryngotracheobronchitis): This condition is characterized by inflammation of the larynx, trachea, and bronchi, leading to a distinctive barking cough, hoarseness, and difficulty breathing. It is more common in young children.

(2) Viral pneumonia: Influenza can directly cause viral pneumonia, where the virus infects the lungs, leading to inflammation and fluid accumulation. Symptoms include severe cough, high fever, difficulty breathing, and chest pain.

(3) Secondary bacterial infections. These usually occur after the initial viral infection. Common bacteria involved include:
🦠 Haemophilus influenzae
🦠 Streptococcus pneumoniae
🦠 Staphylococcus aureus

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14
Q

List non-pulmonary complications of Influenza.

A

(1) Myositis
(2) Cardiac complications
(3) Encephalopathy
(4) Guillain-Barre syndrome [rare neurological disorder where the body’s immune system mistakenly attacks the peripheral nerves]
(5) Reye’s syndrome [a rare but serious condition that causes swelling in the liver and brain, often associated with aspirin use in children recovering from viral infections like the flu: vomiting, confusion, seizures, loss of consciousness]

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15
Q

Briefly discuss diagnosis of Influenza. [specimen and tests]

A

Specimen: throat/nasal swabs, nasal washes

Tests:
🩺 Antigen detection tests: low sensitivity (60%), high specificity (90%)
🩺 PCR
🩺 Serologic Tests e.g. Immunofluorescence tests, ELISA
🩺 Hemagglutination-Inhibition Assay: This assay measures the ability of antibodies to prevent the agglutination (clumping) of red blood cells by the influenza virus.
🩺 Virus Neutralization Assays: These assays measure the ability of antibodies to neutralize the infectivity of the influenza virus. They are sued to assess the immune response to the virus.
🩺 Viral culture

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16
Q

Anti-influenza agents

Uncoating inhibitors

A

Amantadine, Rimantadine (only for Influenza A)

Further notes:
â—¾ Amantadine and rimantidine inhibit the M2 protein of the influenza A virus.
â—¾ Due to widespread resistance, amantadine is no longer recommended for treating influenza A.

17
Q

Anti-influenza agents

Viral release (neuraminidase) inhibitors

A

Oseltamivir, Zanamivir, Peramivir

18
Q

Anti-influenza agents

RNA Polymerase inhibitors

A

Ribavirin, Favipravir

19
Q

Anti-influenza agents

Endonuclease inhibitor

A

Baloxavir