Influenza: Videos & Practice Problems

Influenza A virus, an RNA virus with segmented genome and glycoprotein spikes hemagglutinin (H) and neuraminidase (N), causes respiratory infections. Its subtypes, like H1N1 and H3N2, are named by these antigens. Antigenic drift involves small mutations causing seasonal flu variations, while antigenic shift results in major changes, potentially causing pandemics by mixing genomes from different hosts. Transmission occurs via respiratory droplets. Diagnosis includes rapid antigen tests and PCR. Treatment involves antivirals like oseltamivir and supportive care. Annual multivalent vaccines target predicted strains, adapting to antigenic changes to enhance immunity and reduce morbidity.

Influenza

Influenza, commonly known as the flu, is a viral infection that primarily affects the respiratory tract, often beginning in the upper respiratory tract but capable of involving the entire respiratory system. It is caused by an RNA virus belonging to the Orthomyxoviridae family, characterized by a single-stranded, antisense, segmented RNA genome. This segmentation means the viral genome is divided into multiple RNA segments, resembling mini chromosomes, which is a distinctive feature of the influenza virus.

The virus is enveloped and displays two critical glycoprotein spike proteins on its surface: hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin facilitates viral entry by enabling the virus to recognize and bind to host cells, while neuraminidase assists in viral release from infected cells, promoting the spread of infection. These spike proteins are essential for the virus's virulence and are key targets for immune responses and antiviral drugs.

There are three main types of influenza viruses relevant to human health: types A, B, and C. Influenza A and B are responsible for seasonal epidemics, with type A being the most studied due to its potential for significant variation and pandemics. Influenza C is generally milder and less common. Influenza A viruses are further classified based on the variations in their hemagglutinin and neuraminidase proteins, leading to subtypes such as H1N1, H2N2, and H3N2. This classification is crucial for understanding flu biology and epidemiology.

The flu spreads primarily through respiratory droplets and aerosols, transmitted via direct or indirect contact. Symptoms typically include fever, chills, headache, muscle aches, and respiratory issues like coughing. Unlike some misconceptions, influenza rarely causes gastrointestinal symptoms such as vomiting or diarrhea, which are more characteristic of other illnesses often mistakenly called "stomach flu."

Diagnosis can be made using rapid antigen tests, which have become widely accessible for home use, especially following advancements during the COVID-19 pandemic. Polymerase chain reaction (PCR) testing remains a more sensitive method used mainly for public health surveillance to track circulating strains and variants.

Treatment for influenza generally involves supportive care, including rest and hydration. Antiviral medications such as oseltamivir and zanamivir can be prescribed, particularly for high-risk individuals, and are most effective when administered early in the course of illness. These antivirals can reduce symptom severity and duration.

Immunity against influenza is primarily achieved through annual vaccination with a multivalent flu vaccine, which typically includes protection against two strains of influenza A and two strains of influenza B. The vaccine composition is updated yearly based on predictions by public health officials about the most likely circulating strains. Although the vaccine is generally effective, antigenic changes in the virus can sometimes lead to mismatches, reducing vaccine effectiveness. Nevertheless, vaccination usually provides partial protection even against unmatched strains, underscoring its importance in flu prevention.

Understanding the mechanisms of antigenic variation in influenza A, including how hemagglutinin and neuraminidase proteins evolve, is vital for grasping why annual vaccination is necessary and how new flu strains emerge. This knowledge forms the foundation for ongoing efforts in flu surveillance, vaccine development, and antiviral strategies.

Which of the following types of influenza are the most common and cause seasonal epidemics?


i. Influenza A.
ii. Influenza B.
iii. Influenza C.

• A. I & II.
• B. I & III.
• C. II & III.
• D. I, II, & III.

Answer: (A)

Which of the following is most directly responsible for the entry of the influenza virus into the cell?

• A. The hemagglutinin protein.
• B. The NA spike protein.
• C. Influenza C.
• D. The neuraminidase antigen.

Answer: (A)

Immunity to influenza is acquired through:

• A. Childhood vaccination schedule.
• B. An annual multivalent vaccine.
• C. Community exposure since no vaccine currently exists.
• D. mRNA vaccines each flu season.

Answer: (B)

Flu Naming, Antigenic Drift & Shift

The influenza A virus is classified based on its two key surface antigens: hemagglutinin (H) and neuraminidase (N). These spike proteins determine the virus subtype, such as H1N1, H2N2, or H3N2, where the numbers indicate specific variants of the hemagglutinin and neuraminidase proteins. While there are over ten known subtypes for each protein, only a few, like H1N1 and H3N2, currently circulate widely among humans. Historically, H2N2 was also common but no longer spreads in the human population.

For the influenza virus to continue infecting people, it must evade the immune system's memory, which typically protects against previously encountered viruses. This evasion occurs through two main mechanisms: antigenic drift and antigenic shift.

Antigenic drift refers to the gradual accumulation of small mutations in the virus's surface antigens. These minor changes slightly alter the hemagglutinin and neuraminidase proteins, allowing the virus to partially escape immune detection. This process explains why seasonal flu strains vary year to year and why flu vaccines require regular updates. Importantly, antigenic drift does not change the virus's subtype designation; for example, an H1N1 virus remains H1N1 despite these small mutations.

In contrast, antigenic shift involves a sudden, major change in the virus's surface antigens, often resulting from the reassortment of genetic material between different influenza viruses infecting the same host, such as a pig. Because the influenza virus has a segmented RNA genome, segments from human, swine, or avian flu viruses can mix, creating a novel virus with a new combination of hemagglutinin and neuraminidase proteins. This new subtype can evade existing immunity in the population, potentially leading to pandemics. Historical examples include the 1918 influenza pandemic and the 2009 swine flu outbreak.

An illustrative case of antigenic shift is the emergence of the H3N2 virus in 1968, which replaced the previously dominant H2N2 strain. This new subtype had not circulated in humans for a long time, so the population lacked immunity, resulting in widespread illness and millions of deaths. Since then, H3N2 has continued to evolve through antigenic drift, causing seasonal flu outbreaks but not pandemics.

Understanding the dynamics of antigenic drift and shift is crucial for tracking influenza virus evolution, predicting outbreaks, and developing effective vaccines. The virus's ability to change its hemagglutinin and neuraminidase proteins underlies its persistence and the ongoing challenge of influenza prevention.

Influenza Example 1

The 1968 influenza pandemic introduced the H3N2 flu strain, marking a significant shift from the previously dominant H2N2 strain. This change occurred due to the emergence of a novel hemagglutinin (HA) spike protein variant, specifically the H3 subtype, which was new to humans at that time. Although the neuraminidase (NA) spike protein subtype N2 remained consistent before and after 1968, the introduction of the H3 hemagglutinin represented a major antigenic shift. This shift is characterized by a sudden and substantial change in the virus's surface proteins, often resulting from genetic reassortment, such as the mixing of avian and human flu strains in pigs, which facilitated the creation of this new variant.

Hemagglutinin plays a crucial role in the influenza virus's ability to infect host cells. It is responsible for recognizing and binding to receptors on the surface of respiratory epithelial cells, enabling the virus to gain entry into the cell. This spike protein's structure largely determines the virus's virulence and infectivity. In contrast, the neuraminidase spike protein facilitates the release of newly formed viral particles from infected cells, allowing the infection to spread.

The 1968 pandemic exemplifies antigenic shift rather than antigenic drift. Antigenic drift involves gradual accumulation of small mutations in viral genes, leading to minor changes in surface proteins and typically causing seasonal flu variations without changing the virus subtype designation. Antigenic shift, however, involves a more abrupt and significant change, such as the replacement of one hemagglutinin subtype with another, resulting in a new influenza subtype like H3N2. This process can lead to pandemics due to the population's lack of immunity to the novel hemagglutinin variant.

Most years, a new version of the seasonal flu vaccine is required because of:

• A. Antigenic drift.
• B. Antigenic shift.
• C. Hemagglutinin reshuffling.
• D. Neuraminidase reshuffling.

Answer: (A)

The flu pandemics of 1957, 1968, 2009, and likely 1918 all involved the introduction of either HA or NA protein variants from either birds, swine, or both. Which of the following is a reasonable explanation as to why such an introduction could be associated with a pandemic?

• A. Antigenic shift introduced novel antigens for which humans had no immune defenses.
• B. These pandemics represent zoonoses, which are inherently more dangerous than other infections.
• C. Avian and swine variants of influenza more closely resemble human influenza type C, meaning they are significantly more virulent.
• D. Introduction of a novel NA protein would allow the flu virus to enter new types of cells, significantly increasing its virulence.

Answer: (A)

Here’s what students ask on this topic:

What are the main types of influenza viruses and how do they differ?

Influenza viruses are mainly categorized into three types: A, B, and C. Influenza A and B are responsible for seasonal epidemics, with Influenza A being the most studied due to its ability to cause pandemics. Influenza A viruses have a segmented RNA genome and two key surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA), which are used to subtype the virus (e.g., H1N1, H3N2). Influenza B also causes seasonal flu but is less variable and generally less severe. Influenza C is rare and usually causes mild or no symptoms, so it is less of a concern. The main difference lies in their genetic variability and impact on human health, with Influenza A being the most variable and potentially dangerous.

How do hemagglutinin and neuraminidase proteins function in the influenza virus lifecycle?

Hemagglutinin (HA) and neuraminidase (NA) are two critical glycoproteins on the surface of the influenza virus. HA facilitates viral entry by recognizing and binding to receptors on host respiratory cells, allowing the virus to enter and infect the cell. NA, on the other hand, helps the virus exit the infected cell by cleaving sialic acid residues, which prevents the newly formed viruses from sticking to the host cell surface. This release is essential for the virus to spread and infect other cells. Together, these proteins play key roles in the infection cycle and are targets for antiviral drugs and vaccines.

What is antigenic drift and how does it affect influenza virus evolution and vaccine design?

Antigenic drift refers to the gradual accumulation of small mutations in the influenza virus's surface proteins, hemagglutinin (HA) and neuraminidase (NA). These minor changes alter the virus enough to evade the immune system's memory from previous infections or vaccinations, leading to seasonal flu outbreaks. Because of antigenic drift, the influenza virus changes slightly each year, which is why flu vaccines must be updated annually to match the most common circulating strains. This process explains why immunity to the flu is not lifelong and why repeated vaccination is necessary.

What is antigenic shift and why is it associated with influenza pandemics?

Antigenic shift is a sudden, major change in the influenza virus's surface antigens, resulting from the reassortment of gene segments between different influenza viruses, often from different species like birds, pigs, and humans. Because the influenza virus has a segmented RNA genome, when two different strains infect the same host cell, they can exchange segments, creating a novel virus with new hemagglutinin (HA) and/or neuraminidase (NA) proteins. This new virus can evade existing immunity in the human population, potentially causing widespread illness and pandemics, such as the 1918 and 2009 flu pandemics.

How is influenza diagnosed and what are the current testing methods?

Influenza diagnosis can be done using rapid antigen tests and PCR (polymerase chain reaction) testing. Rapid antigen tests detect viral proteins and can provide results quickly, often within minutes, and are now available for at-home use, similar to COVID-19 tests. PCR testing is more sensitive and specific, detecting viral RNA, and is primarily used by public health officials to monitor circulating strains and variants. While rapid tests are useful for quick diagnosis and treatment decisions, PCR is the gold standard for confirming influenza infection and tracking epidemiology.

What treatments are available for influenza and who should receive antiviral medications?

Treatment for influenza primarily involves supportive care such as rest and hydration. Antiviral medications like oseltamivir (Tamiflu) and zanamivir can be prescribed, especially for individuals at higher risk of complications, such as the elderly, young children, pregnant women, and those with chronic health conditions. These antivirals are most effective when started early in the course of illness and can reduce the duration and severity of symptoms. For otherwise healthy individuals, antivirals may be used but are not always necessary. Preventive measures like annual vaccination remain the best strategy to reduce influenza impact.

Why is the influenza vaccine updated annually and how is it formulated?

The influenza vaccine is updated annually because of the virus's ability to undergo antigenic drift, causing small changes in its surface proteins hemagglutinin (HA) and neuraminidase (NA). Public health officials monitor circulating strains worldwide and predict which variants are most likely to spread in the upcoming flu season. The vaccine is typically multivalent, protecting against multiple strains—usually two Influenza A subtypes and two Influenza B strains. This annual update ensures the vaccine matches the most common circulating viruses, providing effective immunity. Even if the match is not perfect, the vaccine often offers partial protection against related strains.