Influenza Viruses Notes

Learning Objectives

• Relay the taxonomy and types of influenza viruses and explain subtypes identification.
• Describe the clinical course of influenza infection (symptoms, complications).
• Identify influenza protein functions and outline the viral replication cycle stages.
• Explain antigenic drift/shift principles and their implications, including historical antigenic shifts.
• Compare pathogenicity and receptor tropism of human vs. avian influenza viruses.

Influenza Taxonomy and Types

• Enveloped, segmented -ssRNA viruses.


• Family: Orthomyxoviridae.

• Influenza A virus (Genus: Alphainfluenzavirus)
• Influenza B virus (Genus: Betainfluenzavirus)
• Influenza C virus (Genus: Gammainfluenzavirus)
• Influenza D virus (Genus: Deltainfluenzavirus)

• Influenza A:

  • Hosts: Humans, birds, pigs, etc.
  • Gene segments: 8
  • Proteins: 12+
  • Clinical features: Causes pandemics, moderate to severe illness.

• Influenza B:

  • Hosts: Humans, seals, etc.
  • Gene segments: 8
  • Proteins: 11
  • Clinical features: Milder disease, no pandemics.

• Influenza C:

  • Hosts: Humans, pigs, dogs, etc.
  • Gene segments: 7
  • Proteins: 9
  • Clinical features: Generally subclinical.

• Influenza D:

  • Hosts: Primarily cattle.
  • Gene segments: 7
  • Proteins: 9
  • Clinical features: No documented human cases.

• Subtypes of Influenza A:

  • Determined by two envelope glycoproteins: Hemagglutinin (HA), Neuraminidase (NA).
  • 18 HA subtypes (H1-H18) and 11 NA subtypes (N1-N11).
  • Combinations like H1N1, H3N2 circulate in humans.

Clinical Course of Infection

• Transmission: Respiratory droplets from coughs/sneezes, or direct/indirect contact with secretions.
• Symptoms (1-4 days incubation):
  • Fever (101˚F - 102˚F), myalgia, malaise, fatigue, headache, sore throat, rhinorrhea, dry cough.
  • Lasts 3-5 days but cough/ fatigue can persist for weeks.
• Viral Shedding: Begins 1 day before symptoms; children can shed for >10 days.
• Complications: Higher risk in children, elderly, and those with chronic conditions. Most severe complications can include secondary bacterial infections leading to pneumonia.

Molecular Virology

• Virion Structure:

  • Enveloped, pleomorphic, with a helical -ssRNA genome.
  • Contain segmented genome: 8 segments in A/B, 7 in C/D.

• RNP Complex Composition: Each RNA segment associated with nucleocapsid protein (NP) and viral polymerase proteins (PA, PB1, PB2).

• Proteins:

  • M1: Major matrix protein, assists in RNP export.
  • M2: Ion channel involved in membrane fusion.
  • HA and NA: Essential for viral attachment and release. HA is cleaved into HA1 and HA2.

Virus Replication Cycle

1. Attachment: HA binds to sialic acid on respiratory epithelium.
2. Penetration/Uncoating: Endocytosis, followed by fusion of viral and endosomal membranes.
3. Replication: Viral mRNA transcription and genome replication conducted by RdRp.
   • Cap-snatching mechanism from host mRNA for transcription.
4. Assembly: Happens at the plasma membrane, M1 protein assists in RNP recruitment leading to budding.
5. Release: Viral release through NA activity.

Genetic Changes in the Influenza Genome

• Antigenic Drift: Accumulation of mutations leading to new strains (not subtypes) affecting vaccine efficacy.
• Antigenic Shift: Reassortment allows new subtypes to form, raising pandemic risk due to lack of immunity.

Historical Antigenic Shifts

• 1918 Pandemic: Historians mark it as the deadliest, caused by an avian-like H1N1 virus.
• Subsequent pandemics:
  • 1957 H2N2, 1968 H3N2, 1977 H1N1 resurgence.

Highly Pathogenic Avian Influenza (HPAI)

• Circulates in bird populations with increased zoonotic transmission risk.

  • The first known case of H5N1 in humans was in 1997 in Hong Kong, highlighting risks associated with avian influenza.

• Tropism: Differences in receptor binding (α-2,6 for humans, α-2,3 for birds) indicate potential virulence in humans.