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    Keeping watch

    Richard Webby, PhD, (far left) listens as Jon McCullers, MD, speaks to
    the media during a press conference about the H1N1 pandemic.

    As home to the only World Health Organization collaborating center focusing on the transmission of animal influenza viruses to humans, St. Jude is closely monitoring the H1N1 pandemic.

    In late April 2009, a mounting threat moved swiftly through communities worldwide. Newspaper headlines and 24-hour cable news anchors speculated about problems of pandemic proportion. Each day, the World Health Organization (WHO) added dots to a map, signifying the menacing spread of influenza A (H1N1), originally called swine flu.

    The St. Jude Children’s Research Hospital Infectious Diseases department has a long and storied history with influenza research. For faculty and staff in that department, it seemed that the moment they had been preparing for had come.

    “In the beginning stages, there were more things that we didn’t know about this virus than what we did know,” says Richard Webby, PhD, director of the WHO laboratory at St. Jude. “We have not seen this particular combination of genes in the same virus.”

    Seeking answers

    At the pandemic’s start, St. Jude received samples of the virus for testing from the Centers for Disease Control and Prevention (CDC). At press time, the WHO states that more than 94,500 cases of H1N1 infection have been reported worldwide, including 429 deaths. Thus far the virus, although contagious, typically does not cause severe illness and manifests as a mild case of the flu. Symptoms are similar to regular human flu and include fever, cough, sore throat, body aches, headache, chills and fatigue.

    While there is a sense of relief that the H1N1 strain is not as virulent as some influenza virus outbreaks of the past century, St. Jude researchers are as busy as ever. A team of 50 St. Jude faculty and staff, specializing in different areas of study, have assembled to investigate the new strain.

    The virus’ emergence raises many questions that have yet to be answered. And the size of the threat H1N1 poses cannot be determined yet. By their very nature, viruses are crafty organisms, ever changing and evolving. Scientists agree that of the many unknowns, perhaps the biggest is how deadly H1N1 could become.

    “With the H1N1 swine influenza spreading, we are in a situation where we must prepare with maximum urgency for the worst-case scenario—keeping in mind that the virus may wither and wane by this fall and become a wimp or become a monster,” says Robert Webster, PhD, who holds the hospital’s Rose Marie Thomas Chair in Infectious Diseases.

    Drawing on experience

    St. Jude, home to some of the world’s most renowned scientists studying infectious diseases, is one of the five WHO collaborating centers across the world and the only one that focuses solely on the transmission of animal viruses to humans. In 2007, St. Jude was named one of six Centers of Excellence for Influenza Research and Surveillance funded by the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health.

    Along with its work in monitoring the highly virulent H5N1 strain, as well as studying influenza pandemics of the past, St. Jude has researched H1N1 strains for years.

    “We know the biology of this group of viruses,” Webby says.
    “At least one of the parents of this virus has unique characteristics and has done exceptionally well in terms of adapting and growing in swine, and now it’s doing the same thing in humans.”

    Influenza viruses are seemingly simple organisms—segments of RNA, enclosed in protein capsules surrounded by a globular envelope of proteins. The uncomplicated structure makes it especially flexible and able to mutate as it moves from host to host. This constant evolution is why scientists have to create new vaccines for human flu every winter.

    Given the opportunity and time, some flu viruses learn to hop from one species to another—and that’s where the scenario becomes more complicated.

    “There is an enormous diversity of influenza viruses of all shapes and all different flavors,” Webby says. “When viruses get into hosts, such as humans, pigs and certain birds, they evolve along with these hosts, picking up genetic signatures. We can look at an influenza virus and, through genetic sequencing, determine what hosts that virus came out of.”

    Looking back, planning ahead

    Four main influenza type A virus subtypes have been isolated in pigs: H1N1, H1N2, H3N2 and H3N1. The current H1N1 outbreak combines strains of human, avian and swine flu, with pigs serving as the mixing vessel for the viruses.

    The most deadly outbreak caused by an influenza virus was the 1918 pandemic of Spanish flu, which killed more than 40 million people worldwide, about 2.5 percent of Earth’s population at the time.

    St. Jude researchers have long looked at past outbreaks to understand the factors that contribute to influenza’s spread and severity as well as to sequence the viruses’ genomes to identify the mutations that can signal pandemics.

    At the first signs of the current outbreak, scientists were tempted to draw parallels between the 1918 pandemic and the most recent H1N1 infections. In both cases, the virus strikes healthy, younger groups rather than older populations who are normally at risk for the flu. Timing of the two viruses is also worrying. Both surfaced in the spring, rather than during the winter, when flu viruses usually thrive. The 1918 strain, like the new H1N1 virus, originally manifested with mild sickness, but returned in the fall with a vengeance.

    Webby believes it is too early to speculate on a repeat performance. “There is nothing yet to suggest that this would do the same,” he says. “And there is nothing yet to suggest that it would do anything different.”

    The race for researchers now is to find answers.

    “We are continuing to monitor these strains to see if there is any evidence of them changing,” Webby says. “We are becoming particularly interested in the virus’ epidemiology. It looks like there is pre-existing immunity within the human population and particularity in older people. The older population has had more exposure to the H1 viruses. This one virus has a cousin in the human population now.”

    St. Jude scientists are working on genome sequencing for the virus and vaccine development. They are also researching the effectiveness of seasonal vaccines and are continuing their surveillance of the disease’s spread.

    “It is coming up to the winter season in the Southern Hemisphere,” Webby says. “H1N1 is exploding through Australia, and we’ll be able to get a better feel for what it’s going to do in the next few months.”

    Reprinted from Promise Summer 2009

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