Viruses [Specific]

What is the structure of the Influenza genome?

• Eight segments of single-stranded RNA

  • 3 RNA segments → 3 different polymerases → Enzyme complex i.e. RNA-dependent RNA polymerase

  • Other 5 segments → Haemagglutinin, neuraminidase, nucleoprotein, matrix protein M1 and non-structural proteins

• Negative strand → Sequence of viral RNA genome is complementary to sequence of (positive) viral mRNA

• Packaged with protein into a helical nucleoprotein form

What is the structure of the Influenza envelope?

• Derives lipid bilayer from the plasma membrane of the host cell

• Haemagglutinin (glycoprotein) and neuraminidase (enzyme) are embedded in the envelope

  • Different types of haemagglutinin and neuraminidase give rise to different strains of influenza virus

What happens during attachment of the Influenza virus?

• Protruding glycoproteins bind to specific receptor molecules on surface of the host cell

• In humans, haemagglutinin binds to the sialic acid receptor on the host cell membrane

What happens during penetration and uncoating of the Influenza virus?

1. Virus enters by endocytosis

   • Host plasma membrane invaginates and pinches off

2. Virus is placed in an endocytic vesicle → Fuses with lysosome, causing pH to drop in the vesicle to a low pH environment

3. Viral envelope is stimulated to fuse with lytic bilayer of the vesicle membrane

4. Nucleocapsid is released into cytoplasm

What happens during replication of the Influenza virus?

• Viral genome is used as a template to synthesise the viral mRNA (+ strand) catalyzed by viral RNA-dependent RNA polymerase

• mRNA produced acts as a template for synthesis of new viral RNA genome

• mRNA exits the nucleus to the cytosol and rER → Translated into viral structural components such as glycoproteins → Incorporated into the viral envelope (at ER) and capsid proteins (cytosol)

What happens during maturation of the Influenza virus?

• Viral glycoproteins are transported by vesicles from the ER and incorporated into the plasma membrane

• Capsid proteins then associate with these glycoproteins at the plasma membrane

• Viral genome associates with proteins to form helical nucleoprotein which interacts with the capsid proteins at the plasma membrane of the host cell → Initiates budding process

What happens during release by budding of the Influenza virus?

• Virus buds from cell via evagination

  • Virus acquires host membrane with viral glycoproteins embedded

  • With enveloped viruses, host cells may or may not be lysed

• Release is facilitated by neuraminidase

  • Neuraminidase cleaves sialic acid from cell surface and progeny virions facillitating virus release from infected cells

What are the stages of Influenza virus reproductive cycle?

1. Attachment

2. Penetration and uncoating

3. Replication

4. Maturation

5. Release

What is the target organ for Influenza virus?

Epithelial cells of the respiratory tract

How do neuraminidase and haemagglutinin affect humans?

• Respiratory disease

• Virus settles on mucous membrane lining respiratory tract → Neuraminidase enzyme on the surface of viruses helps them penetrate mucoproteins (glycoproteins) in the mucus layer

• Haemagglutinin of the virus binds to specific receptors on the cell membrane of the epithelial cell lining → Virus penetrates host cells → Virus replicates inside

How does the Influenza disease occur after interaction with Influenza virus?

• Infected epithelial cells are destroyed and die → Buildup of dead cells + inflammation in the airway → Runny nose + Scratchy throat

• Weakening of epithelial layer makes the respiratory passage more susceptible to secondary bacterial infections → Pneumonia possibly

• Transmitted via moisture from lungs or infected bird droppings

What are the treatment options for the Influenza virus?

• Antibiotics to prevent secondary bacterial infection (e.g. pneumonia)

• Vaccinations

• Antiviral drugs

  • Neuramidase inhibitors e.g. Tamiflu (oseltamivir) and Relenza (zanamivir)

  • Blocking viral ion channel e.g. amantadine and rimantadine