Pandemic Influenza Virus (A and B)

An influenza pandemic is a global outbreak of a new Influenza virus in people that is very different from current and recently circulating seasonal Influenza viruses. Influenza pandemics happen rarely. Four influenza pandemics have happened in the past 100 years. The four pandemic viruses include the 1918 (“Spanish influenza”) H1N1 virus, the 1957 (“Asian influenza”) H2N2 virus, the 1968 (“Hong Kong influenza”) H3N2 virus, and the 2009 (“swine influenza”) H1N1 virus. The shortest inter-pandemic interval is 11 years, longest interval is 39 years. Pandemic influenza viruses pose a significant threat to public health worldwide.

Fig.1 Timeline of the history of influenza virus circulation in humans since the 1890s. (Francis, 2019)

Respiratory Viral Disease and Symptoms

Fig.2 Influenza A, B, and C virus structure. (Francis, 2019)

Influenza virus is not a single virus but, instead, a family of constantly changing virus strains. Influenza viruses are enveloped virions in helical capsids of approximately 100nm in diameter that contain 7 to 8 single-stranded RNA segments of negative polarity in a nucleoprotein complex, each carrying an RNA-dependent RNA polymerase. Influenza is an enveloped virus that belongs to the family Orthomyxoviridae. According to the current taxonomy, the Orthomyxoviridae family contains the genus Influenza virus and four species, named A, B, C, and D. Influenza C rarely causes human infections, and influenza D viruses mostly infect cattle and will not be further discussed. Both type A and B consist of eight negative-sense, single-stranded RNA segments: polymerase acidic (PA/PA-X), polymerase basic 1 (PB1/PB1-F2), polymerase basic 2 (PB2), hemagglutinin (HA), nucleoprotein (NP), neuraminidase (NA), matrix protein 1 and 2 (M1/M2), non-structural protein 1 (NS1), and nuclear export protein (NEP/NS2).

• Influenza viruses A. Influenza A viruses are further subtyped based on the two major antigens: HA (H1-H18) and NA(N1-N11), which are responsible for host receptor binding/cell entry and cell exit, respectively. Sporadic and unpredictable global pandemic outbreaks occur that involve influenza A virus strains of zoonotic origin.
• Influenza viruses B. Influenza B viruses are found only in humans. Influenza type B viruses are not classified by subtype and do not cause pandemics.

Influenza Virus Pathogenicity

The virus enters through the nasopharyngeal region by droplets expelled by speaking, sneezing, or coughing, by contact with contaminated material or hands. The host cell binding is via the HA that binds to the sialic acid receptor. The incubation time is 1 to 3 days. The virus multiplies rapidly and spreads to neighboring cells. It causes cellular necrosis and apoptosis, altering the ciliar activity and increasing mucus secretion. To exit and infect other cells, NA reduces the viscosity of mucus film breaking sialic acid residues. The damage to the epithelium causes respiratory symptoms and signs, stimulates the natural response of the tract, and promotes bacterial incorporation. The inflammation process can damage bronchi, bronchioles, and alveolar regions. All these events cause initial symptoms of infection like fever, chills, muscle aches, headache, anorexia, and prostration. In pandemics and severe cases, it has been observed that the immune response is exacerbated and may cause greater damage. Importantly, experimental studies suggest that influenza viruses not only increase the severity of secondary bacterial infections but also increase the transmission of S. pneumoniae.

The Future of Pandemic Influenza

• Time: Pandemic influenza occurs every 10-50 years and is characterized by the introduction of a new influenza A virus strain that is antigenically very different from previously circulating strains.
• Variation: Antigenic changes in post-pandemic influenza viruses are associated with antigenic drift, which introduces new epitopes or new glycosylation sites, and by intrasubtypic reassortment of an antigenically different HA of the same subtype.
• Distribution. It’s not possible to predict who would be most at risk of severe complications in a future pandemic. In some past pandemics, healthy young adults were at high risk for developing severe flu complications. During pandemics, influenza viruses spread very quickly from the point of origin to the rest of the world in several waves during the year.
• Mortality. The lack of pre-existing immunity in humans is often associated with the severity of the infection and an increase in mortality.

Prophylaxis and Treatment

Antivirals and vaccines are required to curb the effects of a pandemic. The two main classes of antiviral drugs used against influenza are neuraminidase inhibitors, such as zanamivir and oseltamivir, or inhibitors of the viral M2 protein, such as amantadine and rimantadine. These drugs can reduce the severity of symptoms if taken soon after infection and can also be taken to decrease the risk of infection. The vaccine can induce protection against severe disease following influenza virus infection. The vaccine may not be widely available in the early stages of a pandemic. Rapid vaccine production also remains a challenge for future influenza virus pandemics.

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Reference

1. Francis, M.E.; et al. Back to the Future for Influenza Preimmunity-Looking Back at Influenza Virus History to Infer the Outcome of Future Infections. Viruses. 2019. 11(2): 122.

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