Flu and Pandemic Emergence Quiz

Flu and Pandemic Emergence

• Flu, specifically the influenza virus, is a key example of pandemic emergence and host adaptation.
• Factors contributing to novel pandemic emergence are varied.
• Novel influenza pandemics pose a significant threat.
• Recombination plays a vital role in creating novel influenza viruses.
• H5N1 viruses are a concern as potential pandemic threats.
• Antivirals and vaccines are available for influenza.
• Pandemic emergence is linked to changes in the virus's structure, specifically the hemagglutinin (HA) and neuraminidase (NA) proteins.
• Understanding the different types of sialic acid linkages (α2,3 vs. α2,6) and cleavage sites is crucial in determining virus spread.
• The viral polymerase (PB1, PB2 and PA) adaptations are also influencing the zoonotic transfer of the virus

Definitions

• Epidemic: A significant rise in cases of a disease within a particular region over a specific period, exceeding usual levels.
• Pandemic: A global spread of a disease, affecting a large percentage of the population, originating from a novel pathogen.

Risk of Emergencies in the UK

• A table highlighting relative impact scores for various risks of civil emergencies in the UK, including COVID-19.
• COVID-19 is a relatively high-impact, high-likelihood event.

Source of Pandemics

• Pandemics arise from interactions between humans and wildlife, especially in areas with high biodiversity and rapid human population growth.
• Animal reservoirs like bats, pigs, birds (avian influenza) and other animals can transmit diseases to humans initiating a pandemic.
• Deforestation and land-use changes disrupt natural habitats, increasing human-animal contact and risk of spillover events.

Outbreaks with Pandemic Potential

• Various viruses, including SARS-CoV, H5N1, H7N9, H9N2, MERS, Ebola, and Zika, illustrate potential pandemic outbreaks.
• Increased human interaction with animal reservoirs increases zoonotic spillover risk.

Emerging Zoonotic Diseases

• Deforestation and land-use changes in previously forested areas can create pathways for zoonotic diseases.
• High biodiversity levels in wildlife increase the risk of pathogen spillover.
• Interactions between dense human populations and wildlife accelerate possible spillover events.
• Zoonotic diseases can be caused by various pathogens like influenza (e.g., avian H5N1), MERS-CoV, and Ebola virus.
• Emergence of these diseases highlights the intricate interplay between wildlife, human activities and pathogens.

Pathogens Causing Pandemics

• A pie chart showing that viruses are a significant factor in the occurrence of pandemics, followed by bacteria.
• RNA viruses with high mutation rates pose a specific danger.
• Viruses with segmented genomes show the potential for reassortment and increased virulence.

Influenza Pandemic Frequency

• Influenza viruses, specifically influenza A viruses (RNA viruses), have a high mutation rate compared to other viruses, making them prone to emerging variants.
• High mutation rate and segmented genome contributes to the frequency of influenza pandemics.

Influenza: Respiratory Disease

• Influenza, a highly contagious respiratory illness, presents with symptoms including fever, headache, body aches, sore throat, runny nose, coughing, and sometimes vomiting.
• Complications include pneumonia, miscarriage, premature birth, infant/maternal fatalities.
• The influenza virus primarily infects respiratory tract cells and can cause inflammation and other complications in addition to the common symptoms.

Influenza Transmission

• Influenza can spread among humans through direct contact with infected individuals, contact with contaminated objects, or inhalation of virus-laden aerosols.
• Sporadic cases of human infection from animal sources have been reported, and it's a particular concern for avian influenza.
• Influenza transmission rates vary with the specific strain.

Influenza Virus Entry Sites

• Influenza viruses primarily infect the ciliated cells of the upper respiratory tract, bronchus, and bronchioles, often remaining confined to the lungs.

Seasonal and Pandemic Flu

• Seasonal Epidemics: A limited, regularly occurring winter flu outbreak is mostly non-fatal, with a substantial number of cases.
• Pandemics: Unpredictable, rapid-onset flu outbreaks with significantly higher infection and death rates than seasonal epidemics. Symptoms are generally more serious.

Influenza Virus Families

• The family of influenza viruses includes A, B, C and D, with A-Virus subtype being of notable pandemic potential.
• The unique characteristics of the different types of influenza viruses are important in understanding their prevalence among mammals.

Influenza Virus Structure

• Detailed structure and composition of the virus encompassing the lipid envelope, ribonucleoprotein, and various proteins like HA (hemagglutinin), NA (neuraminidase), M1, M2, and NEP.

Influenza Virus Pleomorphism

• Influenza viruses present in different shapes.

RNA Polymorphism Arrangement

• Details of how the RNA segments are arranged in the virus.

Influenza Virus Lifecycle

• Description of the various stages in the virus life cycle, including entry, replication, and release from the host cell.

Influenza A Virus Subtypes

• Classification of influenza A viruses based on the two surface proteins, haemagglutinin (HA) and neuraminidase (NA).
• Antibodies targeting one subtype generally don't recognize others.

Antibodies and Antigenic Sites

• Antibodies bind to specific antigenic sites on HA and NA proteins, crucial for the virus' recognition by the host's immune system and host-specific responses.

Influenza Viruses in Humans

• A timeline illustrating historical influenza outbreaks and pandemics in human populations, highlighting the recurring nature of the virus (e.g. H1N1, H2N2, H3N2 outbreaks and pandemics)
• The influenza viruses have a recurring pattern in human populations, and this is closely linked to the evolution and reassortment of strains.

Reassortment as a Pandemic Mechanism

• Gene reassortment between different influenza viruses in co-infected hosts plays a key role in producing pandemic viruses.
• Animal-to-human transmission of these reassortant viruses contributes to the beginning of a pandemic.
• Reassortment of gene segments, such as HA and NA segments, from other animal viruses into human strains are key in the emergence of a new pandemic strain.

Avian Viruses and Pandemic Potential

• Avian influenza viruses like H5N1 and others can directly infect humans, posing a pandemic threat, particularly when they reassort with other strains.
• Avian influenza strains have been noted to undergo mutations that facilitate easier human infection.

Antigenic Drift and Shift

• Antigenic drift: gradual changes in surface proteins (like HA and NA), leading to viral adaptation for recurring infection and epidemics.
• Antigenic shift: major changes in virus surface proteins from animal viruses, usually through reassortment with existing strains, creating new pandemic strains.
• Antigenic variations are important factors in the ability of influenza virus strains to adapt in the human population, affecting the spread of the virus.

2009 Swine Flu Pandemic

• The 2009 H1N1 pandemic originated via gene reassortment in pigs.
• Compared to other historical pandemics, this one had a relatively moderate impact.
• The 2009 H1N1 pandemic highlights the potential for spillover of viruses from animal to human hosts with subsequent spread in the human population.

Mortality and the 1918 Pandemic

• 1918 influenza pandemic had significant global mortality.
• 1918 flu pandemic caused a disproportionate number of deaths among relatively younger adults due to various factors, including susceptibility and immune response issues.

Lung Pathology

• Differences in lung pathology between healthy lungs and those infected with the 1918 influenza virus are evident from micrographs depicting inflammation, damage, and cellular responses.

Immune Response

• The innate immune response—recognizing pathogens by pattern recognition receptors, generating interferon responses, and initiating local inflammation—is the initial defense against influenza.
• The adaptive immune response—producing antibodies and T cells targeting specific influenza antigens—provides longer-term protection.
• A "cytokine storm" can occur as part of the immune response in some cases, compounding illness.
• Immune responses to the influenza virus vary across different individuals and groups in the human population.

H5N1 Pandemic Threat

• H5N1 flu kills chickens rapidly.
• Causes severe, multi-system disease, including pneumonia, encephalitis, and other health issues, in both birds and humans.
• Mortality rates exceeding 50% have been observed in human cases.
• H5N1 avian flu has shown adaptability to the human host over recent years.

H5 Avian Influenza

• H5N1 viruses primarily affect birds, with human infections generally resulting from close contact.
• Human-to-human spread has not consistently occurred.
• Human H5N1 cases have highlighted the risk associated with close interaction with infected avian populations.

High Pathogenic vs. Low Pathogenic Flu

• High pathogenic avian influenza (HPAI): Avian flu types that pose a greater threat to poultry health, leading to higher mortality rates.
• Low pathogenic avian influenza (LPAI): A less severe avian flu type usually causing very little or no harm to poultry.
• Differences in virulence and pathogenicity determine whether or not a strain is HPAI or LPAI.

Viral Adaptation for Human Spread

• Viruses must adapt to spread consistently from human-to-human, progressing through specific evolutionary steps, including variations in HA, NA and other structural components.

Haemagglutinin Protein (HA) and Adaptation

• The hemagglutinin (HA) protein is a key factor in influenza virus adaptation.
• HA binds to sialic acid receptors on host cells to facilitate entry.
• HA characteristics are crucial in determining the range of hosts a virus can infect.

Avian vs. Human Sialic Acid Linkages

• Avian form: Viruses that primarily affect birds utilize α2,3-linked sialic acid to bind with host cells.
• Human form: Viruses that affect humans better utilize α2,6-linked sialic acid for cellular entry.

HA Cleavage by Proteases

• The HA0 molecule is cleaved into HA1 and HA2 to facilitate entry inside the host cells by cellular proteases.
• Cleavage characteristics affect whether the infection is restricted to the lungs or spreads systemically.
• Low pH changes the structural conformation of HA, aiding the fusion of virus and host cells for infection.
• Cleavage of HA0 into HA1 and HA2, and the host cell protease's interaction with the virus, is essential for infection.

RNA Polymerase Adaptation

• The RNA polymerase subunits, particularly PB2, are a key factor in allowing the virus to interact with different host cells, influencing host specificity.
• Viral polymerase adaptations can contribute to a wider range of hosts and increase spread in a population.

Ongoing Threat of H5N1

• Globally, H5N1 avian influenza has caused multiple outbreaks in human populations since 2003.
• While human-to-human transmission is not frequent, the rate of spread is a concern, as are potential mutations in influenza strains.

Other Highly Pathogenic Avian Viruses

• Other influenza subtypes, e.g., H5N8, H5N6, and H7N9, also exhibit high virulence and zoonotic potential.
• Newer strain development is a concern, as other bird-specific influenza show pandemic potential.

Antivirals

• Drugs target influenza virus M2 ion channels, neuraminidase activity, or polymerase activity.

M2 Ion Channel Inhibitors

• Amantadine and rimantadine are influenza M2 ion channel inhibitors, blocking viral replication.
• They prevent the acidification needed for viral RNA release into the host cells.

Neuraminidase Inhibitors

• Drugs, such as Tamiflu and Relenza, target neuraminidase, preventing viral release from infected cells.

Polymerase Inhibitors

• Drugs like baloxavir marboxil (Xofluza) and favipiravir block the polymerase activity needed for viral replication in the host cell.

Influenza Vaccines

• Inactivated vaccines are developed from inactivated viruses and require regular updates.
• Live attenuated vaccines use weakened viruses to stimulate immunity.
• Pre-pandemic vaccines may be useful for preparing for the next pandemic. Certain H5N1 vaccines are examples and hold promise.

Summary of Influenza

• Influenza is an RNA enveloped virus that can cause seasonal epidemics and pandemics, with the risk of pandemic emergence affected by different factors, such as mutations in HA, NA and polymerase activity, and human-wildlife interaction.
• Reassortment is pivotal to the emergence of pandemic strains.
• Effective antivirals and vaccines exist but need tailoring for pandemic response.

Wider Reading

• Important publications provide additional context and information for students researching Influenza.
• The available literature emphasizes the need for ongoing surveillance and research to combat and prepare for future pandemic threats.