{"id":4569,"date":"2009-02-14T11:31:33","date_gmt":"2009-02-14T11:31:33","guid":{"rendered":"http:\/\/scienceblogs.com\/gregladen\/2009\/02\/14\/innate-immune-response-defines\/"},"modified":"2009-02-14T11:31:33","modified_gmt":"2009-02-14T11:31:33","slug":"innate-immune-response-defines","status":"publish","type":"post","link":"https:\/\/gregladen.com\/blog\/2009\/02\/14\/innate-immune-response-defines\/","title":{"rendered":"Innate Immune Response Defines Pathology and death in Those Infected by Highly Pathogenic Influenza"},"content":{"rendered":"

\"ResearchBlogging.org\"<\/a><\/span>For the last couple of decades, perhaps beginning around the time of the publication of Laurie Garret’s excellent thesis (The Coming Plague: Newly Emerging Diseases in a World Out of Balance<\/a>\"\") on disease and politics and continuting through Gina Kolata’s “Flu: The Story Of The Great Influenza Pandemic”<\/a>\"\" there has been increased attention on the 1918 flu virus and pandemic, as well as subsequent outbreaks. This interest has probably been fueled by increased knowledge of (or incidence of?) tragic and highly newsworthy outbreaks of Ebola, SARS, and so on. More recently, the perception has grown that the Bird Flu is a’comin’ any time now to ultimately replace the Great Pandemic of 1918 as well as the mud shark in our mythology.<\/p>\n

If you read the better done public-oriented literature of this period, you will learn that the nature, cause or origin, and pattern of the 1918 epidemic has been very mysterious. The same level of mystery (but with only a few victims) arose in connection with the Swine Flu threat of the 1970s (see expecially Garret’s book for how this event links to current attitudes as well as public policy regarding vaccines).<\/p>\n

This brings us to some time last year or so, when key papers were published (and I presume presented at conferences) regarding what may ultimately be seen as the most important single step in the history of understanding the way the flu vaccine works, and thus, how to combat it. (See this<\/a> to explore one of those key moments in research history.)<\/p>\n

The new knowledge is essentially an improved evolutionarily and developmental understanding of how influenza virus strains change over time. To put it very simply, these viruses are made of chunks that come apart in the host and then recombine. If there are multiple ‘strains’ (think species, more or less) of influenza in an individual, these genetic chinks, each representing a huge percentage of the influenza genome, can and do re-combine to form entirely new strains.<\/p>\n

That is in a sense macro-evolution of a pathogen in situ, in the host. What is an immune system to do!?!!?!?? Not much, really. This can be very fatal.<\/p>\n

It is now understood that these epidemic or pandemic influenza outbreaks arise from these recombination events. If you now look back at the quirky data, the odd logic influenza seemed to be patterned by, the epidemiological dead ends that seemed to confound everyone through the lens of knowledge of these genetic chunks, called “reassortants,” things suddenly become much much clearer.<\/p>\n

A paper has just come out in PNAS reporting research using a primate model to explore immune response and associated pathology under the influence of a recombinant influenza virus, and this research is a direct outcome of this new way of looking at the flu. I offer it here without comment largely because you can get the article yourself, since this one is an OpenAccess piece from the normally not OpenAccess PNAS. Here<\/a>.<\/p>\n


\nThe Abstract from the paper:<\/p>\n

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.<\/p><\/blockquote>\n

C. R. Baskin, H. Bielefeldt-Ohmann, T. M. Tumpey, P. J. Sabourin, J. P. Long, A. Garcia-Sastre, A.-E. Tolnay, R. Albrecht, J. A. Pyles, P. H. Olson, L. D. Aicher, E. R. Rosenzweig, K. Murali-Krishna, E. A. Clark, M. S. Kotur, J. L. Fornek, S. Proll, R. E. Palermo, Carol. L. Sabourin, M. G. Katze (2009). Early and sustained innate immune response defines pathology and death in nonhuman primates infected by highly pathogenic influenza virus Proceedings of the National Academy of Sciences<\/span> DOI: 10.1073\/pnas.0813234106<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

For the last couple of decades, perhaps beginning around the time of the publication of Laurie Garret’s excellent thesis (The Coming Plague: Newly Emerging Diseases in a World Out of Balance) on disease and politics and continuting through Gina Kolata’s “Flu: The Story Of The Great Influenza Pandemic” there has been increased attention on the … Continue reading Innate Immune Response Defines Pathology and death in Those Infected by Highly Pathogenic Influenza<\/span> →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"1","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[],"tags":[4630,162,4387,103,3585,2858,4631],"jetpack_sharing_enabled":true,"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/p5fhV1-1bH","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/posts\/4569"}],"collection":[{"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/comments?post=4569"}],"version-history":[{"count":0,"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/posts\/4569\/revisions"}],"wp:attachment":[{"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/media?parent=4569"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/categories?post=4569"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/gregladen.com\/blog\/wp-json\/wp\/v2\/tags?post=4569"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}