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Small Change in 1918 Influenza Virus Halts Transmission
“A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission.”
Tumpey TM, Maines TR, Van Hoeven N, et al.
Science 2007.
CDC researchers and their colleagues used an animal (ferret) model to identify molecular properties of the 1918 pandemic influenza virus that affect its ability to spread. They found that altering two amino acids in one of the surface proteins of the virus stopped its ability to transmit from ferret to ferret.
Understanding which properties of the 1918 virus are important for transmission provides helpful information for the evaluation of future pandemic threats. The findings of this work were published in the February 5 issue of Science in an article entitled “A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission”.
The following questions and answers address this research and related issues.
On this page:
Background on the Research
What research does the Tumpey et al., Science article describe?
In this study, CDC researchers analyzed and experimented with one of the proteins covering the surface of the 1918 influenza virus. They discovered a molecular property that may help to explain the virus’s ability to spread easily from human to human. The researchers’ findings suggest that hemagglutinin (HA), a type of protein found on the surface of influenza viruses and that binds to host cells, plays an important role in the transmission efficiency of the H1N1 pandemic virus. By changing two amino acids (which are the basic building blocks of proteins) in the hemagglutinin of the 1918 virus, CDC researchers were able to create a version of the 1918 virus that was incapable of transmission between ferrets.
Why did the researchers use ferrets in this study?
Ferrets were used in the study because the illness that ferrets get from influenza closely mimics human influenza illness, and the ability of influenza viruses to spread between ferrets also appears to be similar to that in humans (see Maines et al.).
What previous research has CDC done on the 1918 virus?
In October 2005, CDC researchers and colleagues published an article in Science entitled, “Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus, ” which described the successful recreation of a virus matching all eight genes of the 1918 pandemic virus. Since that time, CDC has continued to study the 1918 virus in an effort to better understand the biological and molecular properties that caused its extreme virulence and transmissibility. To date, the factors that lead to the creation of a pandemic virus are complex and poorly understood. However, this research is improving understanding of the molecular properties responsible for the 1918 viruses’ ability to spread rapidly around the globe.
Why is CDC studying the 1918 Virus?
The ability of the 1918 virus to spread rapidly and cause high rates of illness among humans has made it a useful tool for study, particularly for understanding characteristics of influenza viruses that predict their ability to spread easily and cause severe disease in humans. The establishment of efficient and sustained human-to-human transmission of a virus to which humans have little or no immunity is a basic property of pandemic influenza viruses. The 1918-1919 pandemic killed as many as 50 million people worldwide. By forming a better understanding of the molecular characteristics of the 1918 virus, specifically the ones that made it so virulent and easily transmissible, CDC researchers can work to protect against the spread of other influenza viruses with pandemic potential.
What has been learned from research on the 1918 virus?
Research into the 1918 virus using ferrets has indicated that hemagglutinin protein plays an important role in a virus’s ability to spread. This research suggests that for an influenza virus to spread efficiently the virus’s hemagglutinin must prefer attaching to cells that are found in the human upper airway instead of cells found predominately in the respiratory and gastrointestinal tracts of birds. The findings also suggest that viruses that have hemagglutinin capable of attaching to both human and bird cells equally (without preference for either) would not likely spread easily among humans.
Could a 1918-like H1N1 virus re-emerge and cause a pandemic again?
While it is impossible to predict with certainty, it is unlikely that the 1918 virus could re-emerge from a natural source. A portion of the human population shows some evidence of residual immunity to the 1918 virus, or a similar virus. Since modern H1N1 viruses circulate widely and the annual influenza vaccines contain an H1N1 component, a 1918-like H1N1 virus would not fit the criteria for a new pandemic strain. If a pandemic were to occur, it would most likely be caused by an influenza subtype to which there is little, or no, existing immunity in the human population.
How are these findings helping us to prepare for a possible avian influenza A (H5N1) pandemic?
The avian influenza A (H5N1) virus, which is a highly pathogenic strain of influenza responsible for more than 260 human deaths worldwide since 2003, lacks the ability to spread efficiently from human to human. The study by Tumpey et al., however, was conducted using the 1918 virus, which is very different from the H5N1 virus. The specific changes that would need to occur in the H5N1 virus to confer efficient human to human transmission are not known. Efficient transmission of avian influenza viruses in mammals likely would require changes in the hemagglutinin plus additional changes in other virus genes.
Biosafety Precautions
Are there any risks to the public from the experiments being done on this virus?
No. The work described in this article was carried out under stringent biosafety and biosecurity precautions designed to protect workers and the public from possible exposure to this virus.
What biosafety and biosecurity precautions for protecting laboratory workers and the public were in place while this work was being done?
All viruses containing one or more gene segments from the 1918 influenza virus were generated and handled in accordance with biosafety guidelines of the Interim CDC-NIH Recommendation for Raising the Biosafety Level Laboratory Work Involving Noncomtemporary Human Influenza Viruses. All procedures were carried out using the heightened elements mandated by CDC’s Select Agent program.
What are the appropriate biosafety practices and containment conditions for work with the 1918 strain of influenza?
Biosafety Level 3 or Animal Biosafety Level 3 practices, procedures and facilities, plus enhancements that include special procedures (see the question below), are recommended for work with the 1918 strain. There are four biosafety levels that correspond to the degree of risk posed by the research and involve graded levels of protection for personnel, the environment and the community. Biosafety Level 1 provides the least stringent containment conditions, Biosafety Level 4 the most stringent. These biosafety levels consist of a combination of laboratory practices and techniques, safety equipment, and laboratory facilities that are appropriate for the operations being performed. The specific criteria for each biosafety level are detailed in the CDC/NIH publication Biosafety in Microbiological and Biomedical Laboratories.
What is Biosafety Level 3 “Enhanced?” What are the specific enhancements used for work with the 1918 strain of influenza?
A Biosafety Level 3 facility with specific enhancements includes primary (safety cabinets, isolation chambers, gloves and gowns) and secondary (facility construction, HEPA filtration treatment of exhaust air) barriers to protect laboratory workers and the public from accidental exposure. The specific additional (“enhanced”) procedures used for work with the 1918 strain include:
- Rigorous adherence to additional respiratory protection and clothing change protocols;
- Use of negative pressure, HEPA-filtered respirators or positive air-purifying respirators (PAPRs);
- Use of HEPA filtration for treatment of exhaust air; and
- Amendment of personnel practices to include personal showers prior to exiting the laboratory.
Further details of the biosafety recommendations for work with various human and animal influenza viruses, including 1918 virus, can be found in the interim CDC/NIH guidance.
- Page last modified February 5, 2007
- Content Source: Coordinating Center for Infectious Diseases (CCID)
- National Center for Immunization and Respiratory Diseases (NCIRD)
