Tweet
<TABLE cellSpacing=0 cellPadding=27 width="100%" heigth="100%"><TBODY><TR><TD vAlign=top width="100%" height=500 text-align="top">1918 flu virus, recreated in Winnipeg, triggered overwhelming immune response
HELEN BRANSWELL
http://www.cp.org/english/online/Onl...5&languageid=1
(CP) - The virus that caused the 1918 influenza pandemic triggered an overwhelming immune response that swamped the lungs of macaque monkeys - the first primates deliberately infected with the Spanish flu virus, Canadian and American scientists reported Wednesday.
The research, done in part at the Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, supports the notion that the virulent flu virus turned the body's immune system against itself. Scientists believe that theory explains how the devastating influenza strain managed to mow down unprecedented numbers of healthy people in the prime of life.
Previous work, done by some of the same scientists, showed mice infected with the virus also experienced this hyper immune response, a so-called cytokine storm. (Cytokines are one of the proteins the immune system makes to fight infection.)
"There was an uncontrolled or aberrant inflammatory response," one of the authors, Dr. Michael Katze of the University of Washington in Seattle, explained in a telephone briefing.
"One possibility (is) . . . instead of protecting the individuals that were infected with the highly pathogenic virus, the immune response is actually contributing to the lethality of the virus."
Discovering how the Spanish flu, an H1N1 virus, killed an estimated 50 million people around the globe isn't an exercise in archeological microbiology. Cracking the mysteries of highly virulent flu strains could help the world prepare to battle the next bad influenza pandemic, said Darwyn Kobasa, a research scientist with the Winnipeg lab and the first author on the paper.
"Not only is the study of interest to understand what happened in 1918 but it's also very relevant today as we possibly prepare for a new influenza pandemic caused by an avian H5N1 virus," said Kobasa, referring to the highly pathogenic flu strain that for more than three years has been decimating poultry flocks in parts of Asia and which has killed over 160 people.
"The H5N1 virus can also cause very serious disease and it appears to do this in a way that's quite similar to the 1918 virus. We think that a greater understanding of the viruses that caused past pandemics will help us predict what might be expected and how to plan to use our knowledge and resources to reduce the impact of a new pandemic."
The research, published in the journal Nature, involved an ambitious project to painstakingly recreate the 1918 virus - only the second time this feat has been achieved. In 2005 scientists at the U.S. Centers for Disease Control made history by becoming the first team to recreate the virus.
The effort that led to this research began a short time later. Yoshihiro Kawaoka, a leading influenza scientist working at the University of Wisconsin, Madison, built each of the virus's eight genes from scratch, using genetic blueprints housed in a public access database.
He then gave the plasmids - the pieces of DNA in which the genes were placed - to scientists in Winnipeg. They then transferred or "transfected" the genes into cell culture, allowing them to reassemble and grow in a process called virus "rescue."
The recreated virus was then used to infect seven macaques housed in a Level 4 laboratory in Winnipeg - the highest level of biosecurity available. The monkeys became so ill they were euthanized after eight days, at which point lung and other tissues were analyzed to chart the damage done.
Katze and his team in Seattle also traced the immunologic system response by analyzing which immune proteins were produced when, and to what levels.
Scientists hope that learning which parts of the immune system overreact to this or other virulent flu viruses could provide clues as to how the process could be interrupted and the damage lessened.
"It suggests if you interrupt the inflammatory chain in the innate immune response, then you might have another tool in your armamentarium," said Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases and an expert in the workings of the immune system.
But while this work is a start, scientists still don't know how to dampen down the immune response without then letting the virus continue to multiply unchecked.
"If the result is, OK, you get less cytokines which will be good in terms of immunopathology - but because of that you get also even higher levels of virus replication which results in tissue damage, then you've solved one problem but you come out with another one," said Adolfo Garcia-Sastre, the microbiologist at New York's Mt. Sinai Medical Center who played an instrumental role in the first project to recreate the 1918 virus, but who was not involved in this study.
</TD></TR><TR><TD text-align="bottom">
HELEN BRANSWELL
http://www.cp.org/english/online/Onl...5&languageid=1
(CP) - The virus that caused the 1918 influenza pandemic triggered an overwhelming immune response that swamped the lungs of macaque monkeys - the first primates deliberately infected with the Spanish flu virus, Canadian and American scientists reported Wednesday.
The research, done in part at the Public Health Agency of Canada's National Microbiology Laboratory in Winnipeg, supports the notion that the virulent flu virus turned the body's immune system against itself. Scientists believe that theory explains how the devastating influenza strain managed to mow down unprecedented numbers of healthy people in the prime of life.
Previous work, done by some of the same scientists, showed mice infected with the virus also experienced this hyper immune response, a so-called cytokine storm. (Cytokines are one of the proteins the immune system makes to fight infection.)
"There was an uncontrolled or aberrant inflammatory response," one of the authors, Dr. Michael Katze of the University of Washington in Seattle, explained in a telephone briefing.
"One possibility (is) . . . instead of protecting the individuals that were infected with the highly pathogenic virus, the immune response is actually contributing to the lethality of the virus."
Discovering how the Spanish flu, an H1N1 virus, killed an estimated 50 million people around the globe isn't an exercise in archeological microbiology. Cracking the mysteries of highly virulent flu strains could help the world prepare to battle the next bad influenza pandemic, said Darwyn Kobasa, a research scientist with the Winnipeg lab and the first author on the paper.
"Not only is the study of interest to understand what happened in 1918 but it's also very relevant today as we possibly prepare for a new influenza pandemic caused by an avian H5N1 virus," said Kobasa, referring to the highly pathogenic flu strain that for more than three years has been decimating poultry flocks in parts of Asia and which has killed over 160 people.
"The H5N1 virus can also cause very serious disease and it appears to do this in a way that's quite similar to the 1918 virus. We think that a greater understanding of the viruses that caused past pandemics will help us predict what might be expected and how to plan to use our knowledge and resources to reduce the impact of a new pandemic."
The research, published in the journal Nature, involved an ambitious project to painstakingly recreate the 1918 virus - only the second time this feat has been achieved. In 2005 scientists at the U.S. Centers for Disease Control made history by becoming the first team to recreate the virus.
The effort that led to this research began a short time later. Yoshihiro Kawaoka, a leading influenza scientist working at the University of Wisconsin, Madison, built each of the virus's eight genes from scratch, using genetic blueprints housed in a public access database.
He then gave the plasmids - the pieces of DNA in which the genes were placed - to scientists in Winnipeg. They then transferred or "transfected" the genes into cell culture, allowing them to reassemble and grow in a process called virus "rescue."
The recreated virus was then used to infect seven macaques housed in a Level 4 laboratory in Winnipeg - the highest level of biosecurity available. The monkeys became so ill they were euthanized after eight days, at which point lung and other tissues were analyzed to chart the damage done.
Katze and his team in Seattle also traced the immunologic system response by analyzing which immune proteins were produced when, and to what levels.
Scientists hope that learning which parts of the immune system overreact to this or other virulent flu viruses could provide clues as to how the process could be interrupted and the damage lessened.
"It suggests if you interrupt the inflammatory chain in the innate immune response, then you might have another tool in your armamentarium," said Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases and an expert in the workings of the immune system.
But while this work is a start, scientists still don't know how to dampen down the immune response without then letting the virus continue to multiply unchecked.
"If the result is, OK, you get less cytokines which will be good in terms of immunopathology - but because of that you get also even higher levels of virus replication which results in tissue damage, then you've solved one problem but you come out with another one," said Adolfo Garcia-Sastre, the microbiologist at New York's Mt. Sinai Medical Center who played an instrumental role in the first project to recreate the 1918 virus, but who was not involved in this study.
</TD></TR><TR><TD text-align="bottom">
? The Canadian Press , 2007
</TD></TR></TBODY></TABLE>
Comment