# 2790
Earlier this week, Arizona State University released an intriguing press release about an upcoming article scheduled to appear in this week's edition of the Proceedings of the National Academy of Science (PNAS).
The press release, entitled Shades of 1918? New study compares avian flu with notorious killer from the past, gave an overview of the work done by Carole Baskin and an interdisciplinary team of collaborators as they studied and compared the pathogenesis of the H5N1 avian flu virus and two genetic reassortant 1918 viruses in non-human primates.
Pathogenesis is one of those twelve-dollar medical words that simply means the step-by-step progression of a disease.
The results were, as they say, sobering.
While the 1918 viruses were highly pathogenic, they were no match for the H5N1 virus. Here is how the press release put it:
The avian virus was found to significantly outpace not only run-of-the-mill influenza but even the highly virulent 1918 ressortants, in terms of its relentless pathogenicity
H5N1 was found to replicate profusely within the first 24 hours, causing severe damage to respiratory tissues while sending the host's innate immune response into a lethal overdrive, reminiscent of the trajectory of the original 1918 virus.
The study, which is now available to read online, is called:
Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus
Published online before print February 13, 2009, doi: 10.1073/pnas.0813234106
Abstract (reparagraphed for readability)
The mechanisms responsible for the virulence of the highly pathogenic avian influenza (HPAI) and of the 1918 pandemic influenza virus in humans remain poorly understood.
To identify crucial components of the early host response during these infections by using both conventional and functional genomics tools, we studied 34 cynomolgus macaques (Macaca fascicularis) to compare a 2004 human H5N1 Vietnam isolate with 2 reassortant viruses possessing the 1918 hemagglutinin (HA) and neuraminidase (NA) surface proteins, known conveyors of virulence.
One of the reassortants also contained the 1918 nonstructural (NS1) protein, an inhibitor of the host interferon response.
Among these viruses, HPAI H5N1 was the most virulent. Within 24 h, the H5N1 virus produced severe bronchiolar and alveolar lesions.
Notably, the H5N1 virus targeted type II pneumocytes throughout the 7-day infection, and induced the most dramatic and sustained expression of type I interferons and inflammatory and innate immune genes, as measured by genomic and protein assays.
The H5N1 infection also resulted in prolonged margination of circulating T lymphocytes and notable apoptosis of activated dendritic cells in the lungs and draining lymph nodes early during infection.
While both 1918 reassortant viruses also were highly pathogenic, the H5N1 virus was exceptional for the extent of tissue damage, cytokinemia, and interference with immune regulatory mechanisms, which may help explain the extreme virulence of HPAI viruses in humans.
The CFR, or Case Fatality Ratio, among known cases of avian flu has run in excess of 60% during the 5 years since it reappeared. That is at least 10 times greater than the mortality rate of the 1918 pandemic.
There are hopes that, should H5N1 gain the ability to transmit easily from human-to-human, it would lose much of this virulence. But there are no guarantees that will happen.
The research presented in this paper paints a picture of a far more pathogenic disease than the 1918 virus. And it revives the `Cytokine Storm' theory, where the body's own immune response damages the lungs and contributes to the the morbidity and mortality of the virus.
There is a lot in this paper (which I've not read completely) to absorb, and as you might imagine, some of it is a bit technical.
Assuming we aren't deluged with breaking news stories, I will try to put together a layman's tour of the paper over the weekend.
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