NIAID Lab Attacks Flu From Different Directions

Jeffery K. Taubenberger, M.D., Ph.D., a senior investigator in the Respiratory Viruses Section of the NIAID Laboratory of Infectious Diseases, is a world-renowned expert on influenza viruses, particularly the strain that caused the infamous 1918 flu pandemic. Today, his laboratory at NIAID studies a number of viruses, including influenza A viruses (IAVs), which are the pathogens that cause yearly flu epidemics and have caused periodic pandemics, such as the 1968 outbreak that killed an estimated one million people.

This negative-stained transmission electron micrograph depicts the structural details of an influenza virus particle. Influenza A and B are the two types of influenza viruses that cause epidemic human disease. Credit: CDC/ Dr. Erskine. L. Palmer; Dr. M. L. Martin

Dr. Taubenberger’s research aims to inform public health strategies on several important aspects of flu: seasonal flu; avian flu, which circulates among birds and has infected humans in the past; swine flu, which circulates among pigs and has infected humans in the past; and pandemic flu, which can arise from numerous sources and spread quickly because humans have little to no immunity to it.

Responding to New Viruses

The emergence of 2009 H1N1 influenza made international headlines as it affected mostly young people in Mexico, the United States, and other parts of the world.

Dr. Taubenberger’s lab is currently studying the 2009 H1N1 flu virus to understand how this strain emerged and to try to identify factors that allow it to spread and cause disease in humans. It is investigating models of how this new virus infects the respiratory tract of animal models and what allows the virus to be transmitted. Additionally, Dr. Taubenberger and his colleagues will be evaluating how exposure to prior strains of flu may contribute to the immune response to this 2009 H1N1 virus.

Taking on Seasonal Flu

Seasonal flu affects most of the general population at some point in their lives. Its incidence increases at regular, expected times during the winter months. These epidemics are estimated by the World Health Organization to cause between 250,000 and 500,000 deaths worldwide each year.

In a recent analysis, Dr. Taubenberger and several co-authors examined 1,302 complete IAV genomes. Their results showed that virus strains do not persist from one flu season to the next; rather, new strains of flu arise each year. Understanding how IAV evolves is central to its surveillance and control. With this study, Dr. Taubenberger and his collaborators have contributed information that could allow public health officials to determine more quickly and accurately which strains of flu to include in the annual vaccine.

For more information, read Study Provides New Understanding of Forces Behind Seasonal Flu Virus Evolution.

Studying Avian Flu

IAVs in humans are thought to be ultimately derived from avian influenza viruses. Dr. Taubenberger and collaborators were able to determine the complete genomic sequences of 167 wild bird IAVs and, based on their observations, proposed that IAVs in wild birds form transient “genome constellations.” These constellations continually reshuffle, making it difficult to predict what prevention methods will work on which strains. Understanding the ecology and evolution of avian IAV is important for pandemic preparedness and to understand how these viruses might adapt to humans.

Researching Swine Flu

IAVs also infect pigs around the world, and different strains of flu viruses have circulated in pigs at least since 1918. Pigs can be infected with flu viruses adapted to pigs, humans, and birds, so they have been called a “mixing vessel” for flu viruses.

Dr. Taubenberger and his collaborators have been studying swine flu in the laboratory and recently published a study of the evolution of different strains of swine flu since 1918. These studies are shedding light on how flu viruses adapt to pigs. His lab is also actively involved in studies evaluating how different swine influenza viruses cause disease in various animal models.

Preparing for a Pandemic

Pandemic flu has led to tremendous loss of life. For example, the 1918 pandemic resulted in the deaths of 40 to 50 million people worldwide. Modern vaccines and health preparations have usually been able to stay ahead of new flu viruses in recent years; however, new pandemic IAVs are an ever-present threat. To prepare for a pandemic, understanding the how’s and why’s of past pandemics is essential.

Dr. Taubenberger, and other co-authors from NIAID, developed a comprehensive analysis of victims of the 1918 pandemic. In addition to studying actual tissue samples from 58 U.S. soldiers who died of influenza between 1918 and 1919, the co-authors identified and reviewed 118 contemporary autopsy series reports on victims of the pandemic, comprising 8,398 individual autopsies conducted in 15 countries. Their results showed that the primary cause of death among the victims was not the influenza virus but rather bacterial pneumonia. Flu weakened the victim’s immune system, allowing the bacteria to invade and kill. This realization promises to make preparations for diagnosing, treating, and preventing bacterial pneumonia a major component of planning efforts for a future pandemic.