Bird Flu: Science and Policy

[Preciouslife1]

Researchers Identify Key Step Bird Flu Virus Takes To Spread Readily In Humans

http://www.medicalnewstoday.com/articles/84869.php

Since it first appeared in Hong Kong in 1997, the H5N1 avian flu virus has been slowly evolving into a pathogen better equipped to infect humans. The final form of the virus, biomedical researchers fear, will be a highly pathogenic strain of influenza that spreads easily among humans. In a new study a team of researchers from the University of Wisconsin-Madison report the identification of a key step the virus must take to facilitate the easy transmission of the virus from person to person. The study, published today in the journal PLoS Pathogens, details how a team of researchers led by virologist Yoshihiro Kawaoka of the UW-Madison School of Veterinary Medicine has identified a single change in a viral protein that facilitates the virus' ability to infect the cells of the upper respiratory system in mammals. This adaptation could allow the virus to infect a wider range of cell types and spread more easily, potentially setting the stage for a flu pandemic.

"The viruses that are in circulation now are much more mammalian-like than the ones circulating in 1997," says Kawaoka, an internationally recognized authority on influenza. "The viruses that are circulating in Africa and Europe are the ones closest to becoming a human virus." There are other yet-to-be-determined changes required for the virus to become a human pathogen of pandemic proportions, Kawaoka explains, but establishing itself in the upper respiratory system is necessary as that enables easy transmission of the virus through coughing and sneezing. As its name implies, bird flu first arises in chickens and other birds. Humans and other animals in close contact with the birds may become infected as the virus begins to adapt to new host animals, a process that may take years as small changes accumulate. Over time, an avian virus may gather enough genetic change to spread easily, as experts believe was the case with the 1918 Spanish flu, an event that killed at least 30 million people worldwide.

To date, more than 250 H5N1 human infections worldwide have been reported. Of those, more than 150 have been fatal, but so far efficient human-to-human transmission has not occurred. Most infections have occurred as a result of humans being in close contact with birds that have the virus, such as chickens.

According to Kawaoka, the avian virus can reside in the lungs of humans and other mammals as the cells of the lower respiratory system have receptors that enable the virus to establish itself. Temperatures in the lungs are also higher and thus more amenable to the efficient growth of the virus.

The new study involved two different viruses isolated from a single patient -- one from the lungs, the other from the upper respiratory system. The virus from the upper respiratory system exhibited a single amino acid change in one of the key proteins for amplification of influenza virus genes.

The single change identified by the Wisconsin study, Kawaoka says, promotes better virus replication at lower temperatures, such as those found in the upper respiratory system, and in a wider range of cell types.

"This change is needed, but not sufficient," Kawaoka explains. "There are other viral factors needed to cause a viral pandemic" strain of bird flu. However, Kawaoka and other flu researchers are convinced it is only a matter of time, as more humans and other animals are exposed to the virus, before H5N1 virus takes those steps and evolves into a virus capable of causing a pandemic.

In addition to Kawaoka, authors of the new PLoS Pathogens study include Masato Hatta, Yasuko Hatta, Jin Hyun Kim, Shinji Watanabe of the UW-Madison School of Veterinary Medicine; Kyoko Shinya of Japan's Tottori University; Tung Nguyen of the Vietnamese National Centre for Veterinary Diagnostics; Phuong Song Lien of the Vietnam Veterinary Association; and Quynh Mai Le of the Vietnamese National Institute of Hygiene and Epidemiology. The work was funded by grants from the U.S. National Institutes of Health and the Japan Science and Technology Agency.

CITATION: Noda T, Ebihara H, Muramoto Y, Fujii K, Takada A, et al. (2006) Assembly and budding of Ebolavirus. PLoS Pathog 2(9): e99. DOI: 10.1371/journal.ppat.0020099