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Influenza is a respiratory infection characterized by fever, cough, and severe muscle aches. In the elderly and infirm, it is a major cause of disability and death (often as a result of secondary infection of the lungs by bacteria). Even in the young and healthy, influenza produces a prostrating disease of a few days duration and one not soon forgotten.Influenza is not
In February 1997, Ann Reid, Jeffery Taubenberger and their colleagues reported (in the 21 March 1997 issue of Science) the partial sequences of 5 influenza genes recovered from the preserved lung tissue of a U.S. soldier who died from influenza in 1918.Why had they bothered? Because:
This electron micrograph (courtesy of Dr. K. G. Murti) shows several influenza virus particles (at a magnification of about 284,000x). The surface projections are molecules of hemagglutinin and neuraminidase (see below).There are three types of influenza:
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The result is a viral pneumonia. It usually does not kill the patient (the 1918 pandemic was an exception; some victims died within hours) but does expose the lungs to infection by various bacterial invaders that can be lethal. Before the discovery of the flu virus, the bacterium Hemophilus influenzae was so often associated with the disease that it gave it its name.
(The pandemic of 1957 probably made more people sick that the one of 1918. But the availability of antibiotics to treat the secondary infections, that are the usual cause of death, resulted in a much lower death rate.)
The hemagglutinin of the 1918 flu virus was H1, its neuraminidase was N1, so it is designated as an H1N1 "subtype". Here are some others.
|1918||being studied||H1N1||pandemic of "Spanish" flu|
|1957||A/Singapore/57||H2N2||pandemic of "Asian" flu|
|1968||A/Aichi/68||H3N2||pandemic of "Hong Kong" flu|
|1976||A/New Jersey/76||H1N1||swine flu in recruits|
These data suggest that flu pandemics occur when the virus acquires a new hemagglutinin and/or neuraminidase. For this reason, when an H1N1 virus appeared in a few recruits at Fort Dix in New Jersey in 1976, it triggered a massive immunization program (which turned out not to be needed).Where do the new H or N molecules come from? No one yet knows.
Missense mutations in the hemagglutinin (H) gene.Flu infections create a strong antibody response. After a pandemic or major epidemic, most people will be immune to the virus strain that caused it. The flu virus has two options:
The gradual accumulation of new epitopes on the H (and N) molecules of flu viruses is called antigenic drift. Spontaneous mutations in the H (or N) gene give their owners a selective advantage as the host population becomes increasingly immune to the earlier strains.
Although a case of the flu elicits a strong immune response against the strain that caused it, the speed with which new strains arise by antigenic drift soon leaves one susceptible to a new infection. Immunization with flu vaccines has proved moderately helpful in reducing the size and severity of new epidemics.Some vaccines incorporate inactivated virus particles; others use the purified hemagglutinin. Both types incorporate antigens from the three major strains in circulation, currently:
Because of antigenic drift, the strains used must be changed periodically as new strains emerge that are no longer controlled by people's residual immunity.
|01-02||A/New Caledonia/99||A/Panama/99||B/Sichuan/99 or similar|
Antibiotics are of absolutely no value against the flu virus. However, they are often given to patients to combat the secondary bacterial infections that occur and that are usually the main cause of serious illness and death.
There are far fewer anti-viral drugs than anti-bacterial drugs because so much of the virus life cycle is dependent on the machinery of its host. There are many agents that could kill off the virus, but they would kill off host cell as well. So the goal is to find drugs that target molecular machinery unique to the virus. The more we learn about these molecular details, the better the chance for developing a successful new drug.
In May of 1997, a 3-year-old boy in Hong Kong died of influenza. It turned out that the virus that killed him was the same one that had been killing chickens in the region but had not been implicated in any human infections. The virus is H5N1. The H5 molecule is common among bird influenza viruses but has never before been seen on flu viruses that cause human disease.
As a glance at the tables above will show, humans have had long experience with infections and vaccines by both H1 and H3 flu viruses. But the human population has absolutely no immunity against any H5 viruses. Was the boy's disease an isolated incident or had the ground been prepared for another worldwide pandemic?Fortunately, it appears that there is little cause for alarm.
Despite this good news, work is going forward on an H5N1 vaccine just in case!
An international team, led by Canadian scientist Dr. Kirsty Duncan, travelled to Longyearbyen, Norway in 1998 to collect tissue samples from the bodies of six miners who died there in 1918, presumably of the "Spanish" flu. It was hoped that the bodies had been buried six feet deep in the permafrost and so would have remained frozen since 1918. However, it turned out that the bodies were in a shallow grave and would have been repeatedly thawed and frozen. Despite that, tissue samples have been removed for analysis in laboratories in Canada, the United States, Great Britain, and Norway. The goal is to attempt to recover fragments of the viral genome in the hope of understanding why that flu virus was so lethal. The samples will be handled under strict conditions of biological containment.
To find out more about this project, the case in Hong Kong, and much more about the flu, read the superlative account by Malcolm Gladwell ("The Dead Zone") in the September 29, 1997 issue of The New Yorker.
As for the sequence analysis by Reid and Taubenberger, their results suggest that the hemagglutinin (H) gene of the 1918 virus came from birds and moved into both humans and pigs.
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