DNA Sequences Analyzed
Clues to the human pathogenicity of the H5N1 strain of influenzavirus A (Hong Kong) have been discovered in studies by Hong Kong, CDC, and USDA workers. In a paper (Science 279:393-396, 1998) by workers at CDC (Subbarao, Klimov, Katz, Regnery, Lim, Hall, Perdue, Swayne, Bender, Huang, Hemphill, Rowe, Shaw, Xu, Fukuda, and Cox [only in America!]), it was reported that the avian influenzavirus A [Hong Kong/156/97 (H5N1)] is comprised of 8 RNA segments derived from avian influenzavirus A. The hemagglutinin contains multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. Experimentally, the virus is highly pathogenic for chickens.
The article reported that the hemagglutinin gene contains an extra piece of RNA, a feature common in avian flu viruses but never before isolated from a human flu virus. It codes for extra amino acids at exactly the point at which the protein is cleaved by enzymes in the body. That is the key step by which the virus gains entry into avian or human cells.
In most flu viruses the enzymes needed to cleave the hemagglutinin are found only in the lungs or digestive tract and most viruses can infect only cells in those organs. But the extra amino acids may make the protein capable of being cleaved by enzymes found in many organs, which then are able to support replication of the virus. Robert Webster, a flu expert at St Jude Children's Research Hospital in Memphis, Tennessee, said that allowed the virus to spread through the blood.
The pathogenicity studies demonstrate that the virus remains lethal to chickens even after it has passed through a human and raises the possibility that a few infected people travelling beyond Hong Kong could spread it to millions of chickens worldwide.
The remaining question is how a bird virus manages to infect human. The US team found one clue by comparing the virus isolated from Hong Kong chickens in March with the isolate from the first case-patient. They found a difference: the loss of a carbohydrate molecule near the point at which the virus binds to cell surfaces. That molecule is present in the avian samples but absent from the virus that infected the case-patient. Dr. Webster speculates that the change "may have great influence" on the virus's ability to bind to human cells.
Fortunately the evidence still is that the virus cannot pass easily between human beings, limiting the chances of a pandemic. Dr. Webster told Science he was satisfied that Hong Kong's millions of chickens in open markets had been slaughtered. "The slaughter was absolutely essential," he said. "The big question is whether it was done in time."
Mainland source ruled out
Virologists have initially ruled out the mainland as the origin of the bird flu virus, pointing the finger at dirty chicken farms and markets in Hong Kong. The 13-member World Health Organisation delegation, on a 10-day mainland visit to discuss the H5N1 crisis with authorities, also said Guangzhou's influenza surveillance programme appeared satisfactory.
"We learned about the Chinese surveillance system at the briefing [with mainland officials] and from what has been said, we think the system is all right," spokesman Dr. Daniel Lavanchy said yesterday. "But we shall go to see how it actually works," he said, adding the team would meet frontline doctors at hospitals and clinics in Guangzhou today.
Dr. Lavanchy said preliminary findings showed no indication that the mainland was the source of the virus, despite reports of suspicious sudden deaths of chickens last year. "Apparently there has not been a case of bird flu in China. But there are several cases in Hong Kong," he said. Barbara Reynolds, one of the Centres for Disease Control scientists in Hong Kong working on the virus, was surprised by Dr. Lavanchy's remarks. "We have nothing to base that on yet," she said, adding she was unaware of a report suggesting the source was in Hong Kong.
CDPC Note: It's hard to rule anything out after the first day of formal meetings! Show me the data! How many virus isolation tests have been carried out to rule out the absence of H5N1 in southern China?
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