A recreated H1N1 flu virus, the same type that caused the 1918 Spanish Flu pandemic. According to researchers, the virus killed by attacking the body's immune system.
Credit: Wikipedia
PARIS: The Spanish flu pandemic of 1918 - the mostly deadly plague of the last century - killed so many because it caused the body's immune system to go haywire, say researchers.
The flu, caused by the H1N1 strain of the virus, broke out among troops in the trenches of the Western Front in World War I, and the pathogen spread to the rest of the world when the troops returned home at the end of the war.
Using a resurrected version of the same virus in a high-security lab, pathologists in the United States tested H1N1 and a 'conventional' flu virus on macaque monkeys. The team obtained their H1N1 virus - which is extinct outside of a few laboratories today - from the tissue of an Alaskan victim of the Spanish flu whose remains had been preserved in permafrost. Fragments of the virus were teased out, allowing the team to painstakingly recreate its eight genes.
Their study, to be published tomorrow in the British journal Nature, discovered that H1N1 killed the monkeys by over-stimulating their immune system. The culprits were alpha and beta interferons, specialised proteins that cause inflammation. Within minutes or hours of infection, these proteins signal the presence of an intruder to the heavy weaponry of the immune system and stimulate its response.
In monkeys infected with the conventional virus, levels of these proteins peaked only briefly and were proportional to the levels of virus. In the monkeys infected with H1N1, though, the proteins ran amok.
According to the research team, led by Yoshihiro Kawaoka of the University of Wisconsin at Madison, over-stimulation of the immune system can make a pathogen more virulent, because the immune cells, when unchecked, start penetrating healthy tissues and destroying them.
By the time the 1918 pandemic had run its course, between 25 and 50 million people around the world had died. The strain was 25 times deadlier than a conventional virus, said the researchers.
One of the biggest riddles is why so many of the victims were adults in the prime of life, rather than the very old and the very young - the typical fatalities in a flu epidemic. The virus was so lethal that it could take a young soldier in robust good health and put him in his grave just a few days later, destroying lung tissue so brutally that the victim would literally drown in his own blood.
The answer to what causes the body's guardians to run loose like this is still hazy, but Kawaoka's team suggested a link with a gene called RIG-1, which controls a protein of the same name that directs the cascade of interferons and other immune system proteins.
Lab tests on tissue infected with the 1918 virus showed that levels of the RIG-1 protein were lower than in tissue infected with the conventional virus: in other words, the molecular controller was somehow stopped from doing its job.
The new research supports work on lab mice last year that pointed the finger at an over-excited immune system, but also at activation of genes that order cells to commit suicide.
The work on H1N1 carries new urgency in the context of concern focussing on the H5N1 bird flu virus. In its present form, bird flu is lethal to poultry, and to humans in close proximity to infected fowl. The worry is that it could acquire the genetic changes that would make it both lethal and contagious among humans.
