Influenza Viruses by James McSharry, PhD

Summary

In this lecture, Professor James Macari discusses influenza viruses, focusing on their structure and replication process. He explains the difference between low and highly pathogenic strains, the current circulating strains like H5N2 and H5N8, and the 2014 outbreak's link to bird migration. Macari also covers antiviral treatments, including ion channel blockers and neuraminidase inhibitors, and the development of vaccines, highlighting the challenges of creating effective vaccines due to the virus's high mutation rate.

Takeaways

• 🦠 Influenza viruses are negative sense, enveloped RNA viruses that infect various species including birds and humans.
• 🌐 Current circulating strains include H5N2 and H5N8, with geographical spread linked to bird migration.
• 🔬 The virus structure consists of two main surface proteins: Hemagglutinin (H) and Neuraminidase (N), which are crucial for viral attachment and release.
• 🌿 H5N1, which first appeared in China in 1997, has mutated into H5N2 and H5N8, causing significant issues in poultry worldwide.
• 🌡 The severity of influenza can range from mild to deadly, with highly pathogenic strains being more deadly due to their ability to infect various organs.
• 🧬 Influenza viruses are typed into A, B, and C based on the antigenic properties of their nucleoprotein and membrane proteins.
• 💊 Antiviral drugs like amantadine and rimantadine target ion channels of the virus, but resistance is a concern.
• 🌐 The 2009 H1N1 pandemic virus spread globally causing a large number of infections, though not as severe as initially feared.
• 💉 Current vaccines include inactivated vaccines and live attenuated influenza virus vaccines, designed to induce antibodies against specific antigens.
• 🔄 The need for annual flu vaccines arises from the constant mutation of the HA protein, necessitating updates to match circulating strains.
• 🔬 Research is ongoing to develop broadly reactive antibodies and vaccines that could provide protection against all influenza strains.

Q & A

What are influenza viruses?

Influenza viruses are negative sense envelope RNA viruses that contain segmented genomes. They infect various hosts including waterfowl, birds, and occasionally spread to humans and other animals, causing diseases that can range from mild to severe or even deadly.

What are the current circulating influenza viruses?

The current circulating influenza viruses mentioned in the script are H5N2 and H5N8.

How did the H5N1 virus spread globally?

The H5N1 virus appeared in China in 1997 and spread throughout the world, mutating into H5N2 and H5N8, which are causing significant problems in poultry today.

What are the two lipoproteins on the exterior of the influenza virus?

The two lipoproteins on the exterior of the influenza virus are the hemagglutinin (H), which is responsible for attaching the virus to cells, and the neuraminidase (N), which facilitates the release of new virus particles from infected cells.

What is the function of the matrix protein (M1) in the influenza virus?

The matrix protein (M1) in the influenza virus is a major structural protein that lies beneath the viral envelope, providing structural support to the virus particle.

How many ribonucleoproteins are contained within the influenza virus?

There are eight ribonucleoproteins contained within the influenza virus, each associated with a segment of the virus's negative-sense RNA genome.

What are the different types of influenza viruses and how are they classified?

Influenza viruses are classified into types A, B, and C based on the antigenic properties of the nucleoprotein (NP) and the matrix proteins (M). Type A viruses are further subtyped based on the hemagglutinin (HA) and neuraminidase (NA) proteins, with 16 known HA subtypes and 9 known NA subtypes.

What is the significance of the cleavage of the hemagglutinin protein in the pathogenicity of avian influenza viruses?

The cleavage of the hemagglutinin protein is significant in the pathogenicity of avian influenza viruses because it determines how easily the virus can spread within a host. Low pathogenic viruses are cleaved slowly by trypsin-like enzymes, limiting their spread to the respiratory and gastrointestinal tracts. In contrast, highly pathogenic viruses can be cleaved by numerous proteases throughout the body, leading to systemic infection and increased virulence.

What is the replication cycle of the influenza virus?

The replication cycle of the influenza virus begins with attachment to host cell receptors, followed by internalization into the cell's cytoplasm. The viral RNA is then released into the nucleus where it is transcribed into mRNA and replicated. New viral components are assembled and the virus particles are released to infect other cells.

What are the two main classes of antiviral drugs mentioned for treating influenza?

The two main classes of antiviral drugs mentioned for treating influenza are ion channel blockers (like amantadine and rimantadine) and neuraminidase inhibitors (like oseltamivir and zanamivir).

What is the purpose of the live attenuated influenza vaccine (LAIV) and how is it different from the inactivated vaccine?

The live attenuated influenza vaccine (LAIV) contains weakened live viruses that are delivered intranasally, providing a mild form of the infection that stimulates an immune response without causing severe illness. It is different from the inactivated vaccine, which contains killed viruses and is administered intramuscularly, typically with a needle.

Why is a new influenza vaccine developed each year?

A new influenza vaccine is developed each year because the hemagglutinin antigen of type A viruses mutates randomly, leading to different antigens annually. This requires the vaccine to be updated to match the circulating strains and provide effective protection.