Influenza Antigenic Drift and Shift
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Direct answer
Influenza antigenic drift and shift are the two ways the virus changes its surface antigens. Drift is gradual point mutation in haemagglutinin and neuraminidase that causes seasonal epidemics, whereas shift is an abrupt reassortment of gene segments that can cause pandemics. Oseltamivir, a neuraminidase inhibitor, is the most widely used antiviral, and it works best when started within 48 hours of symptoms.
What you must remember
- Haemagglutinin: It has 18 H subtypes, binds sialic acid receptors and mediates fusion, and antibodies against it neutralise infection.
- Neuraminidase: It has 11 N subtypes, cleaves sialic acid to release progeny virions, and it is the target of oseltamivir.
- Human subtypes: H1N1, H3N2 and influenza B lineages circulate in humans, with H1N1 and H3N2 the main influenza A subtypes.
- Drift: Point mutations accumulate in the antigenic sites of haemagglutinin, reducing antibody binding and forcing annual vaccine updates.
- Shift: Reassortment between human and avian or swine strains creates a new subtype to which the population has little or no immunity.
- Pandemic history: The 1957 H2N2, 1968 H3N2 and 2009 H1N1 pandemics arose through reassortment of human and animal influenza genes.
- Vaccine strain selection: The WHO reviews surveillance data and recommends vaccine composition for the northern and southern hemispheres each year.
- Antivirals: Oseltamivir and zanamivir inhibit neuraminidase, baloxavir inhibits viral cap-dependent endonuclease, and adamantane resistance is now widespread.
Drift and shift compared
Drift and shift both change the surface antigens, but they differ in mechanism, speed and consequence. The table sets out the contrast that exams most often test.
| Feature | Antigenic drift | Antigenic shift |
|---|---|---|
| Mechanism | Point mutation | Reassortment of gene segments |
| Viruses involved | One lineage changing over time | Two strains in one cell |
| Typical result | Seasonal epidemics | Pandemics |
| Population immunity | Partly retained | Largely absent |
| Vaccine response | Annual strain update | Emergency vaccine development |
Drift is tracked by the haemagglutination inhibition test, which shows how far antiserum against an old strain still blocks a new isolate. A marked drop in inhibition signals an antigenic change that the current vaccine strain may not match, and its results feed directly into the choice of vaccine strain at each WHO meeting.
Shift cannot be predicted year by year, so surveillance of animal reservoirs, particularly pigs and birds, is the main early-warning tool for a novel reassortant. Pigs carry both avian-type and human-type sialic acid receptors, so they can be co-infected with both kinds of virus and act as mixing vessels.
Where the exam tries to catch you
Drift and shift questions usually test the mechanism and the consequence, which students often swap.
- Trap: Assigning pandemics to drift because it is gradual Correct: Pandemics follow shift, because reassortment creates a subtype with little population immunity, whereas drift produces seasonal epidemics.
- Trap: Thinking neuraminidase inhibitors block haemagglutinin Correct: Oseltamivir inhibits neuraminidase, which releases progeny virions from infected cells, so it limits spread rather than entry.
- Trap: Relying on amantadine for influenza A Correct: Adamantane resistance is now widespread in circulating influenza A strains, so these drugs are not used routinely.
Frequently asked questions
Which influenza surface protein mediates attachment and fusion?
Haemagglutinin mediates attachment to sialic acid receptors and membrane fusion, and it is the main target of neutralising antibodies. Its antigenic sites are where point mutations accumulate during antigenic drift.
Which influenza pandemics arose through antigenic shift?
The 1957 H2N2 and 1968 H3N2 pandemics, and the 2009 H1N1 pandemic, arose through reassortment of human and animal influenza genes. Each produced a subtype against which most of the population had little or no immunity.
Why does influenza vaccine need updating every year?
Influenza vaccine must be updated each year because antigenic drift changes the haemagglutinin and neuraminidase antigens that antibodies recognise. The WHO reviews circulating strains and recommends the vaccine composition for the northern and southern hemispheres.
What is the haemagglutination inhibition test used for?
The haemagglutination inhibition test measures how well antiserum against one strain blocks the haemagglutination activity of another, which reveals antigenic differences. A marked drop in inhibition indicates an antigenic change that existing vaccine strains may not match.
Why is oseltamivir started within 48 hours of symptoms?
Oseltamivir works best when started within 48 hours of symptom onset, because it blocks neuraminidase, which the virus needs to release new virions from infected cells. Early treatment shortens the illness and reduces the risk of complications in high-risk patients.