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Dissecting a Deadly Flu
28 August 2002 (All day)
Researchers have identified the gene that may have made a rare flu strain particularly lethal. The strain, which nearly wreaked havoc in Hong Kong 5 years ago, carries a gene whose protein neutralizes the body's first line of defense against invaders.
In 1997, a flu strain called H5N1 that was common in chickens jumped to people in Hong Kong, killing six of the 18 it infected (normally a tiny fraction of those infected by flu die). Authorities isolated the patients and killed all the city's chickens, stemming a potential pandemic. But researchers remained puzzled by the unusual virulence of the strain. One clue was the viral protein called NS1, which hampers the body's first response to invading viruses. Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee, and colleagues noted that the 1997 Hong Kong strain had a tiny alteration in its NS1 protein, and they wondered if that was what made it especially deadly.
The team focused on three molecules that mount the initial offensive against viral invaders: two types of interferons and tumor necrosis factor ? (TNF-?). First, they grew milder flu strains on cultured pig cells. As expected, either interferons or TNF-? could swiftly disable them. But the defenses were useless when faced with the Hong Kong strain. Digging deeper, the researchers then stitched the NS1 gene from the 1997 strain into a mild strain. They report in the 26 August online Nature Medicine that pigs infected with the mild strain recovered within 5 days, but pigs infected with the hybrid virus remained sick for 2 weeks, losing 40% of their weight and becoming lethargic and dehydrated.
"Their data are quite striking and very believable," and drugs that target NS1 could one day keep dangerous strains of influenza in check, says molecular pathologist Jeff Taubenberger of the Armed Forces Institute of Pathology in Rockville, Maryland. But these experiments don't definitively prove that NS1 is the culprit, the human and pig immune systems might react differently to it.