AN EVOLVING ENEMY
ANTIGENIC DRIFT Changes in viral antigens caused by genetic mutation during normal viral replication.
When Kawaoka and his colleagues discovered that the 1918 flu virus carried specific alleles of four genes that enabled the virus to replicate in the lower respiratory tract, thus making the disease so deadly, a piece of the 75-year-old mystery was solved. But where did these alleles come from?
New influenza viruses are constantly being produced by two mechanisms: mutation and gene swapping. Because influenza viruses replicate their genetic material so rapidly and don’t “proofread” the replicated copies, mistakes often occur, leading to mutations. Antigenic drift is the gradual accumulation of mutations that causes small changes in the antigens on the virus surface. Antigenic drift explains why there can be different types, or strains, of influenza circulating at the same time.
Two important antigens on the influenza virus are hemagglutinin (which binds to receptors on host cells and enables the virus to enter host cells) and neuraminidase (which helps new viruses exit host cells). The host immune system mounts an adaptive response specifically to these two antigens. When there is a change in hemagglutinin or neuraminidase or both, the memory cells no longer recognize them. These new antigens prompt a new and slow primary immune response.
ANTIGENIC SHIFT Changes in antigens that occur when viruses exchange genetic material with other strains.
An influenza virus strain can also swap genes with other strains of influenza, including strains that infect animals such as birds and pigs. While every influenza strain contains the same set of genes, the particular alleles of these genes that are present differ from strain to strain. The exchange of alleles between two strains that have infected the same cell does not simply create a small change in viral gene sequence: it introduces an entirely new allele, and therefore an entirely new antigenic protein. This process, called antigenic shift, is responsible for pandemic outbreaks of flu. Because people have no existing immunity to protect against infection by emerging strains of flu, these strains can spread rapidly throughout the human population. The severity of the 1918 flu is believed to have resulted in part from antigenic shift. Antigenic shift is also thought to have played a role in the emergence of avian flu in the 1990s and swine flu (H1N1) in 2009, both of which originated in animals.
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Together, antigenic drift and antigenic shift create an increasing variety of strains over time until one of the variants is able to infect human cells so efficiently that it sweeps through the population and causes a pandemic. These strains are named by the type of H (hemagglutinin) and N (neuraminidase) proteins they carry, with some antigenic combinations more deadly than others (INFOGRAPHIC 31.10).
Mutation and gene exchange are two mechanisms by which influenza viruses can change. Mutations that accumulate gradually can cause variations in surface antigen. This process is called antigenic drift. Different strains can also swap genes and cause surface antigens to change more dramatically. This is called antigenic shift. Drift is responsible for annual seasonal variation in influenza; shift is responsible for dramatic pandemics.
Tracking the strains as they move through the population helps public health officials predict how severe a coming flu season will be. But since viruses can mutate every time they reproduce, they continue to evolve during epidemics. This unpredictability is what makes influenza so frightening: an apparently mild outbreak can suddenly become deadly.
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