Arnold J. Levine Discusses Tracking Influenza Virus Epidemics

Arnold J. Levine, Professor in the School of Natural Sciences at the Institute for Advanced Study, will address influenza epidemics and the related research conducted by The Simons Center for Systems Biology in his talk, Tracking Influenza Virus Epidemics over the Past Century: Can We Predict Next Year's Epidemic?  The lecture will take place on Wednesday, December 5 at 4:30 p.m. in Wolfensohn Hall on the Institute’s campus.
    Influenza viruses are unusual because we can become infected by a similar virus almost every year during our lifetime and occasionally there are worldwide pandemics that can cause many fatalities. Why does our usually excellent immune system fail us? How does this come about?
        The influenza virus contains eight chromosomes that are each made of an RNA molecule. It is an unusual virus in that it may replicate in many animals (such as birds, horses, pigs, camels and whales) and humans.  Influenza viruses have three properties that permit them to change very rapidly: 1. As the RNA chromosomes are replicated during an infection, the mutation rate, or error rate, is very high, changing the virus very often. This is called genetic drift.  2. When two different influenza viruses replicate in the same cell, the eight chromosomes reassort into new progeny viruses creating many new combinations of the two parents. This is called genetic shift. 3. Viruses that replicate for a long time in birds can reassort with human viruses, making hybrids that have never been in humans before (inter-species genetic shift) and this has given rise to three pandemics over the twentieth century.  Thus, the rapid evolutionary changes (drift) and the reassortment of chromosomes during an epidemic (shift) combine with natural selection for viruses never experienced by the immune system of humans in the population, and a new virus is successful in its replication almost every year. 
        The group at The Simons Center for Systems Biology at the Institute has examined the changing sequences of each of the eight chromosomes of influenza virus over the past ninety years and through three pandemics. The group has found certain RNA sequence contexts that preferentially occur in human viruses and others found only in birds. The 1918 epidemic occurred when a bird virus jumped into the human population. The descendants of the 1918 virus have slowly drifted into a human RNA viral sequence over the past ninety years. Surprisingly, this genetic drift has occurred in a non-random fashion. By studying recent epidemics in New York and New Zealand, we have been able to follow genetic shifts of chromosomes. Contrary to present ideas in the field, this also occurs in a non-random fashion. In experiments in cell culture it has been shown that this non-random pattern occurs because of the manner in which the virus packages its eight chromosomes.
        Because drift and shifts occur in a directed fashion, there is some hope of understanding the rules guiding the evolution of this virus, and of being able to predict next year’s virus, and possibly the bird virus that could jump to a human and start a pandemic.  Progress has been made in these areas.
    Professor Levine leads The Simons Center for Systems Biology at the Institute, which concentrates on research at the interface of molecular biology and the physical sciences -- on genetics and genomics, polymorphisms and molecular aspects of evolution, signal transduction pathways and networks, stress responses, and pharmacogenomics in cancer biology.  His research centers on the causes of cancer.  In 1979, he and others discovered the p53 tumor suppressor protein, a molecule that inhibits tumor development.  
    As chair of the National Institutes of Health Commission on AIDS Research and the National Academies Cancer Policy Board, Professor Levine has helped determine national research priorities. 
    For further information about this event, which is free and open to the public, please call (609) 734-8175, or visit the Public Events page on the Institute website, www.ias.edu.