Hni5

PERSPECTIVE

H5N1 influenza viruses: Facts, not fear
Peter Palesea,b,1 and Taia T. Wanga
Departments of aMicrobiology and bMedicine, Mount Sinai School of Medicine, New York, NY 10029 The ongoing controversy over publication of two studies involving the transmission in ferrets of H5N1 (H5) subtype influenza viruses and the recommendations of the National Science Advisory Board for Biosecurityto redact key details in the manuscripts call for an examination of relevant scientific facts. In addition, there are calls in the media to destroy the viruses, curtail future research in this area, and protect the public from such “frightening” research efforts. Fear needs to be put to rest with solid science and not speculation.
avian influenza

| moratorium | World Health Organization | casefatality rate | National Science Advisory Board for Biosecurity
mutations identified in the studies by Fouchier and Kawaoka could cause the viruses to be more transmissible between humans, but this is simply unknowable from the available data. The viruses may well be more adapted to ferrets, but not more adapted to other mammals; one cannot directly extrapolate from the data to make predictionsabout humans. In fact, passage of viruses in a different host is the most frequently used strategy to reduce viral virulence in humans. Many live, attenuated virus vaccines have been generated by that approach, including those for poliovirus and yellow fever virus. Further experiments in other mammalian systems would enhance our understanding of the potential for the H5 viruses to transmit betweennonferret mammals and/or cause disease in these systems (19–21). It is known that H5 viruses have been circulating in poultry for at least 50 years (probably much longer) and that they cause natural infection and even transmit between some mammals such as pigs, dogs, and cats (21–24) (Figs. 1 and 2). Despite regular human contact with animal reservoirs and the virus’ propensity to mutate, strainsable to cause sustained disease in humans have not emerged. In fact, in humans, only influenza viruses of the subtypes H1, H2, and H3 have circulated during the past 100 years, suggesting that other subtypes may not easily become significant human pathogens.
Why Is it Important to Have the Full Data Published? With respect to the specific

Facts
What Are the Studies About? The two studiesdiscussed here are by Ron Fouchier at Erasmus Medical Center in Rotterdam and Yoshihiro Kawaoka at the University of Wisconsin (not yet published by Science and Nature, respectively). Both senior authors are experienced virologists who have worked for years with highly pathogenic avian influenza viruses. Their respective studies differ in many ways, but both were designed to answer one question of whetherH5 influenza viruses can achieve sustainable aerosol transmission in ferrets. The studies use the age-old method of virus adaptation by repeated passage in cells or in naive animal hosts. H5 viruses (WT or with specific mutations introduced that are known to confer tropism to mammalian tissue) were passaged in ferrets, a well established animal model for the study of influenza transmission (1–5).Ultimately, both studies determined that, indeed, H5 viruses could acquire aerosol transmissibility while maintaining virulence in ferrets.* The experiments demonstrate the important finding that aerosol transmission between ferrets can be determined by a relatively small number of mutations that do not significantly change virus virulence. Thus, the need for continued surveillance efforts around H5viruses is clearly reinforced by these works, as is the importance of continuing to develop H5 vaccines and therapeutics (6).
How Relevant Are These Studies for Humans?

resulted in the majority of our scientific and medical achievements. With specific reference to influenza viruses, the free flow of data has enabled the timely development of vaccines and other medications for seasonal and...