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    Antigenic Drift and Antigenic Shift of Influenza Virus Strains
    Research, Experiments and Background Information
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    Research and Experiments

      Definitions

      Antigenic shift occurs when two different virus strains recombine to form a new virus with mixed genome and antigency. Most common in influenza viruses.

      Antigenic drift is the continuous genetic and antigenic change (mutation) of flu and other virus strains.

      Both processes, mentioned above, pose the danger of rendering vaccines against viruses less effective.

      Articles, Studies and Research

    • Influenza Vaccine — Outmaneuvering Antigenic Shift and Drift [View Experiment]
    • The Evolution of Human Influenza Viruses[View Experiment]
    • The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types [View Experiment]
    • Epidemiology and pathogenesis of influenza [View Experiment]
    • Influence of Virus Strain on the Efficacy of Vaccine Against Avian Influenza Virus Subtype H7N3 [View Experiment]

      Theses and Dissertations

    • Preparing for an influenza pandemic: Re-evaluating the use of the whole inactivated virus vaccine formulation - A comparison of the immune responses after intramuscular or intranasal immunization with an influenza H5N1 whole inactivated virus vaccine in a murine model [View Experiment]
    • The immunogenicity of an intranasal adjuvanted pandemic avian influenza vaccine in murine model [View Experiment]
    • Kinetics of influenza a virus infections in a heterogeneous cell population [View Experiment]
    • Alternative Approaches In The Preparation And Growth Of Influenza B Vaccine Viruses [View Experiment]
    • Adaptation of a/mallard/Potsdam/178-4/83 (H2N2) in Japanese quail leads to replication and transmission in chickens [View Experiment]
    Antigenic Drift and Antigenic Shift of Influenza Virus Strains

    Definitions

    Antigenic drift is the mutation of a virus so that its new antigen form is sufficiently different from the old and thus it can evade immunity to the original strain of the virus.

    Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.

    Introduction

    New influenza viruses are constantly evolving by mutation or by reassortment. Mutations can cause small changes in the hemagglutinin and neuraminidase antigens on the surface of the virus. This is called antigenic drift, which slowly creates an increasing variety of strains until one evolves that can infect people who are immune to the pre-existing strains. This new variant then replaces the older strains as it rapidly sweeps through the human population—often causing an epidemic. However, since the strains produced by drift will still be reasonably similar to the older strains, some people will still be immune to them. In contrast, when influenza viruses reassort, they acquire completely new antigens—for example by reassortment between avian strains and human strains; this is called antigenic shift. If a human influenza virus is produced that has entirely new antigens, everybody will be susceptible, and the novel influenza will spread uncontrollably, causing a pandemic. In contrast to this model of pandemics based on antigenic drift and shift, an alternative approach has been proposed where the periodic pandemics are produced by interactions of a fixed set of viral strains with a human population with a constantly changing set of immunities to different viral strains.

    Antigenic Shift

    Antigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. The term is often applied specifically to influenza, as that is the best-known example, but the process is also known to occur with other viruses, such as visna virus in sheep. Antigenic shift is a specific case of reassortment or viral shift that confers a phenotypic change.

    Antigenic shift is contrasted with antigenic drift, which is the natural mutation over time of known strains of influenza (or other things, in a more general sense) which may lead to a loss of immunity, or in vaccine mismatch. Antigenic drift occurs in all types of influenza including influenzavirus A, influenza B and influenza C. Antigenic shift, however, occurs only in influenzavirus A because it infects more than just humans. Affected species include other mammals and birds, giving influenza A the opportunity for a major reorganization of surface antigens. Influenza B and C principally infect humans, minimizing the chance that a reassortment will change its phenotype drastically.

    Antigenic shift is important for the emergence of new viral pathogens as it is a pathway that viruses may follow to enter a new niche. It could occur with primate viruses and may be a factor for the appearance of new viruses in the human species such as HIV. Due to the structure of its genome, HIV does not undergo reassortment, but it does recombine freely and via superinfection HIV can produce recombinant HIV strains that differ significantly from their ancestors.

    Flu strains are named after their types of hemagglutinin and neuraminidase surface proteins, so they will be called, for example, H3N2 for type-3 hemagglutinin and type-2 neuraminidase. When two different strains of influenza infect the same cell simultaneously, their protein capsids and lipid envelopes are removed, exposing their RNA, which is then transcribed to mRNA. The host cell then forms new viruses that combine their antigens; for example, H3N2 and H5N1 can form H5N2 this way. Because the human immune system has difficulty recognizing the new influenza strain, it may be highly dangerous. Influenza viruses which have undergone antigenic shift have caused the Asian Flu pandemic of 1957, the Hong Kong Flu pandemic of 1968, and the Swine Flu scare of 1976. Until recently, such combinations were believed to have caused the infamous Spanish Flu outbreak of 1918 which killed 40~100 million people worldwide; however more recent research suggests the 1918 pandemic was caused by the antigenic drift of a fully avian virus to a form that could infect humans efficiently. One increasingly worrying situation is the possible antigenic shift between avian influenza and human influenza. This antigenic shift could cause the formation of a highly virulent virus.

    For example, if a pig was infected with a human influenza virus and an avian influenza virus at the same time, an antigenic shift could occur, producing a new virus that had most of the genes from the human virus, but a hemagglutinin or neuraminidase from the avian virus. The resulting new virus would likely be able to infect humans and spread from person to person, but it would have surface proteins (hemagglutinin and/or neuraminidase) not previously seen in influenza viruses that infect humans, and therefore to which most people have little or no immune protection. If this new virus causes illness in people and can be transmitted easily from person to person, an influenza pandemic can occur.

    Antigenic Drift

    The immune system recognizes viruses when antigens on the surfaces of virus particles bind to immune receptors that are specific for these antigens. This is similar to a lock recognizing a key. After an infection, the body produces many more of these virus-specific receptors, which prevent re-infection by this particular strain of the virus and produce acquired immunity. Similarly, a vaccine against a virus works by teaching the immune system to recognize the antigens exhibited by this virus. However, viral genomes are constantly mutating, producing new forms of these antigens. If one of these new forms of an antigen is sufficiently different from the old antigen, it will no longer bind to the receptors and viruses with these new antigens can evade immunity to the original strain of the virus. When such a changes occurs, people who have had the illness in the past will lose their immunity to the new strain and vaccines against the original virus will also become less effective. Two processes drive the antigens to change: antigenic drift and antigenic shift, antigenic drift being the more common.

    In the influenza virus, the two relevant antigens are the surface proteins, hemagglutinin and neuraminidase. The hemagglutinin is responsible for entry into host epithelial cells while the neuraminidase is involved in the process of new virions budding out of host cells. The host immune response to viral infection is largely determined by the immune system's recognition of these influenza antigens. Vaccine mismatch is a potentially serious problem. Antigenic Drift is the continuous process of genetic and antigenic change among flu strains.

    To meet the challenge of antigenic drift, vaccines that confer broad protection against heterovariant strains are needed against seasonal, epidemic and pandemic influenza.

    As in all RNA viruses, mutations in influenza occur frequently because the virus' RNA polymerase has no proofreading mechanism, providing a strong source of mutations. Mutations in the surface proteins allow the virus to elude some host immunity, and the numbers and locations of these mutations that confer the greatest amount of immune escape has been an important topic of study for over a decade.

    Antigenic drift has been responsible for heavier-than-normal flu seasons in the past, like the outbreak of influenza H3N2 variant A/Fujian/411/2002 in the 2003 - 2004 flu season. All influenza viruses experience some form of antigenic drift, but it is most pronounced in the influenza A virus.

    Antigenic drift should not be confused with antigenic shift, which refers to reassortment of the virus' gene segments. As well, it is different from random genetic drift, which is an important mechanism in population genetics.

    For more information:
    http://en.wikipedia.org/wiki/Influenza
    http://en.wikipedia.org/wiki/Antigenic_drift
    http://en.wikipedia.org/wiki/Antigenic_shift

    Source: Wikipedia (All text is available under the terms of the GNU Free Documentation License and Creative Commons Attribution-ShareAlike License.)

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