Avian flu could lead to 1918-like Spanish flu pandemic

February 11th, 2009 - 4:41 pm ICT by ANI  

Washington, Feb 11 (ANI): On comparing the recent avian strain with genetic ressortants of the post World War I virus, researchers found that H5N1 could lead to an avian flu pandemic just like the Spanish flu that spread in 1918.
The study was conducted by Carole Baskin, formerly assistant research professor at Arizona’’s Biodesign Institute, currently with Science Foundation Arizona, and an interdisciplinary team of collaborators.
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.
“In order to come up with vaccines and therapies, you have to understand the disease. That’’s why I think this type of pathogenesis study is so important,” stressed Baskin.
The mortality rate for those stricken with highly pathogenic avian influenza (HPAI) H5N1 is 63 percent, and with a series of modifications the virus could pass from person to person, leading to catastrophic consequences for humankind.
In the study, researchers examined the host-pathogen responses to a common influenza virus and two ressortant strains of the 1918 H1N1 virus, each containing HA and NA-key surface antigens closely linked to the 1918 strain’’s potent virulence.
The effects of these strains on host tissues and gene expression were compared with those of a 2004 Vietnam isolate of the Highly Pathogenic Avian Influenza (HPAI) H5N1.
In a non-human primate model of the disease, 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.
Ressortant viruses occur when different influenza subtypes or strains simultaneously infect the same host.
Under these conditions, a shuffling and exchange of genetic material between two or more such viruses can occur, which could give rise to new viral forms which share genetic characteristics with each parent strain but may also possess novel attributes, including heightened virulence.
In both H5N1 and 1918 H1N1, the highly pathogenic strains replicate rapidly and induce a massive transcription of genes associated with the innate immune response, the body’’s first line of defence for combating viral challenges.
The researchers used a systems biology approach to compare the 1918 flu strain with H5N1, and analysed with high-throughput technologies of functional genomics, proteomics and transcriptomics to measure gene expression and regulation in fine-grained detail.
Then they subjected post-infection respiratory tissues to pathological, viral and microarray analysis.
Although the 1918 ressortant strains were found to be highly virulent, they were outmatched by H5N1′’s rapid onset, overwhelming transcription induction of cytokine and chemokine genes and headlong, sustained viral replication with wider distribution in the lungs.
While the new study found that the 1918 ressortant strains and H5N1 each attacked specialized respiratory cells called pneumocytes, the 1918 chimaraes showed preference for so-called type I pneumocytes, responsible for air exchange in the lungs.
On the other hand, H5N1 characteristically infects the more numerous type II pneumocytes, a critical distinction. Thus, H5N1 delivers a devastating one-two punch to the host’’s ability to recover from the infectious siege.
The researchers observed that within 24 hours, H5N1 had caused severe bronchiolar and alveolar lesions in lung tissue.
Also, Tissue sampling for H5N1 found a notable absence of dendritic cells whose job it is to phagocytize protein components from the virus and present these to T cells, either locally or at the lymph nodes that drain the lungs.
The absence suggested they were destroyed during the infection process, which would point to H5N1′’s ability not only to disable the present infection but also to block the body’’s ability to build immunity against later infection by the same type of virus.
Continuing studies of host-pathogen responses at the tissue, cellular and molecular level may provide the understanding needed to stave off a viral pandemic, whether from H5N1 or some other emergent strain.
In terms of how many modifications would be required for H5N1 to become a highly contagious human virus, Baskin said: “There have been some estimations and it’’s not a lot. That’’s the short and simple answer.”
The study appears in the latest issue of the Proceedings of the National Academy of Science. (ANI)

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