Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus

Abstract

The pandemic influenza virus of 1918–1919 killed an estimated 20 to 50 million people worldwide. With the recent availability of the complete 1918 influenza virus coding sequence, we used reverse genetics to generate an influenza virus bearing all eight gene segments of the pandemic virus to study the properties associated with its extraordinary virulence. In stark contrast to contemporary human influenza H1N1 viruses, the 1918 pandemic virus had the ability to replicate in the absence of trypsin, caused death in mice and embryonated chicken eggs, and displayed a high-growth phenotype in human bronchial epithelial cells. Moreover, the coordinated expression of the 1918 virus genes most certainly confers the unique high-virulence phenotype observed with this pandemic virus.

MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

“…In animal models, heterosubtypic cross‐protection against challenge with highly pathogenic H5N1 virus has been observed with influenza vaccines using mucosal adjuvants or immunostimulating complexes 21 , 52 . These data support the view that induction of cross‐reactive antibodies in humans is clinically relevant.…”

“…The disease is now widespread among poultry and migratory birds in many parts of the world and, significantly, more than 380 humans have been infected, with approximately 240 (63%) deaths 18 . Based on the number and severity of human infections, an A/H5N1‐influenza virus is considered by most experts to be the most likely candidate to cause the next pandemic, 19 which is expected to spread quickly and to cause substantial global morbidity and mortality 20 , 21 . Pre‐pandemic vaccination against H5N1 and other strains with pandemic potential could therefore form the first line of defence against pandemic influenza.…”

Detection of Influenza Virus Induced Ultrastructural Changes and DNA Damage

“…The influenza virus M1, NS1, and NA proteins have been reported to be related to apoptosis induction [13,16,30]. Also the importance of HA in apoptotic cell death in vitro is further supported by recent findings showing that the HA of the 1918 pandemic influenza virus enhances mortality in mice [11,18,26].…”

“…Infection of epithelial cells and lymphocytes has been shown to induce apoptosis in vitro [6,14,17,24]. Infection with virulent influenza (H5N1) virus was also shown to induce lymphopenia and lymphocyte apoptosis in vivo [8,25,26]. Apoptosis also plays an important role in the pathogenesis of many infectious diseases, including those caused by viruses, bacteria and prions [1,15,20].…”

Bird-flu research: The biosecurity oversight

“…The first two 3,4 to land in the board's lap, in 2005, dealt with efforts to resurrect the Spanish flu virus that was responsible for millions of deaths immediately after the First World War. The board recommended that the papers be published in full.…”