Washington – Researchers at the U.S. Centers for Disease Control and Prevention (CDC) have devised a method to understand better one of the key questions surrounding the threat of pandemic influenza – how do you know when an animal virus is going to mutate to become contagious among humans?

CDC researchers announced July 31 they have developed better ways to probe that question, and found the virus might not mutate easily from animal to human pathogen. That is good news at a time when the H5N1 strain of avian influenza has spread to bird populations in more than 50 nations, and reached pandemic proportions in some areas, officials say.

“There is an urgent need to better understand how these viruses could acquire the ability to spread efficiently between people,” said CDC Director Dr. Julie Gerberding in a press release. “This research increases our knowledge, and may enable us to more quickly identify H5N1 viruses and other influenza viruses that have the potential to cause a pandemic.”

The H5N1 virus has infected more than 230 people in 10 nations since it swept out of Southeast Asia in 2003, and more than half of those have died. Disease experts have examined most of those human cases closely, and, so far, they do not find that the virus has developed the capability easily to infect humans or to be transmitted efficiently between individuals. That is the threshold the virus must cross if it is to set off a wave of global sickness.

THE EXPERIMENT

One of the ways that the H5N1 virus might mutate to become dangerous to humans is if it entered the system of a person who already was carrying a flu virus known to infect humans and common in the environment. There are more than 25 such viruses identified, formed as the distinctive proteins comprising an influenza virus - hemagglutinin and neuraminidase – arrange themselves in different ways.

For example, if a person carrying an H3N2 virus that usually gives humans the general aches and fever of seasonal flu also becomes infected with an H5N1 virus, then the two viruses might combine in the person’s system and form a hybrid virus. If that hybrid inherits the highly pathogenic qualities of H5N1, and the human transmissibility properties of H1N1, experts fear a potentially killer virus could be born.

The CDC researchers created conditions like these, without using human subjects. They infected ferrets, known to have a susceptibility to flu similar to humans, with trial viruses and kept the animals in close conditions to see if the hybrid virus spread through the population.  It did not.

The human H3N2 strain spread among the animals, but neither the H5N1 nor the new hybrid virus was contagious among the caged ferrets.

“This study provides for the first time an assessment of the risk of an H5N1 pandemic strain emerging through reassortment with a human influenza virus,” said Dr. Jackie Katz, one of the lead researchers of the project. “However, there is still much we do not know about the molecular changes the virus would need to cause a pandemic.”

Katz said researchers need to continue using the research method to see if other possible virus combinations emerge, or if H5N1 might further change to become a greater pandemic threat.

The research was conducted in collaboration with Centro Nacional de Biotecnologia, Madrid, Spain; National Institute of Hygiene and Epidemiology, Hanoi, Vietnam; and the Center for Biomedical and Pharmaceutical Research and Development, Ministry of Health, Jakarta, Indonesia, which provided reagents and viruses for the study.  All laboratory work was conducted at CDC.

The research is reported in the most recent edition of the Proceedings of the National Academy of Sciences.

For ongoing coverage, see Bird Flu (Avian Influenza).