Pathogenicity of Influenza Viruses with Genes from the 1918 Pandemic Virus: Functional Roles of Alveolar Macrophages and Neutrophils in Limiting Virus Replication and Mortality in Mice

摘要: The Spanish influenza pandemic of 1918 to 1919 swept the globe and resulted in deaths at least 20 million people. basis pulmonary damage high lethality caused by H1N1 virus remains largely unknown. Recombinant viruses bearing hemagglutinin (HA) neuraminidase (NA) glycoproteins were rescued genetic background human A/Texas/36/91 (H1N1) (1918 HA/NA:Tx/91) virus. Pathogenesis experiments revealed that HA/NA:Tx/91 was lethal for BALB/c mice without prior adaptation is usually required A viruses. increased mortality HA/NA:Tx/91-infected accompanied (i) (>200-fold) viral replication, (ii) greater influx neutrophils into lung, (iii) numbers alveolar macrophages (AMs), (iv) protein expression cytokines chemokines lung tissues compared with levels seen control Tx/91 virus-infected mice. Because pathological changes AMs neutrophil migration correlated inflammation, we assessed role these cells pathogenesis associated infection. Neutrophil and/or AM depletion initiated 3 or 5 days after infection did not have a significant effect on disease outcome following By contrast, before sublethal uncontrolled growth In addition, decreased chemokines. These results indicate possessing HA NA can induce severe inflammation consisting neutrophils, which play controlling replication spread intranasal