The Pathologic Anatomy of Influenzal Bronchopneumonia

Resurrected Pandemic Influenza Viruses

“…At the high virus inoculum of 10 6 PFU, mice displayed a sudden onset of severe illness and succumbed to infection as early as 3 days following an intranasal inoculation. This NP: nucleoprotein was consistent with the rapid course of disease in some of its human victims who died in 1918 as a result of an overwhelming viral pneumonia (50). Virus titers in lungs of 1918 virus-inoculated mice were nearly 40,000-fold higher than those of mice infected with the contemporary Tx/91 virus (103).…”

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

“…Histological observations of archived fixed tissues from 1918 showed heavy infiltrations of white blood cells into influenza-infected lungs, including the alveoli, suggesting that such cells were involved in the pathogenesis of disease (35,71,72). The studies described herein were based on a previous observation that the lethal 1918 HA/NA:WSN recombinant influenza virus and the nonlethal New Caledonia HA/NA:WSN control virus induced markedly different patterns of mouse lung inflammation (30).…”

“…Approximately 30% of the world's population was clinically infected during the pandemic (15), and there was an unusually high lethality rate among healthy adults aged 15 to 34 years, a finding that has not been observed in subsequent pandemics or epidemics caused by influenza A viruses (40). Histopathological analysis of lung tissues from individuals who died from primary influenza pneumonia in 1918 showed massive pulmonary edema with unique destruction of the alveolar architecture (35,58,72). The retrieval of viral RNA from archived autopsy materials and from the body of an Alaskan influenza victim buried in permafrost has revealed the genetic code of this H1N1 subtype influenza virus.…”

Intranasal Vaccination with 1918 Influenza Virus-Like Particles Protects Mice and Ferrets from Lethal 1918 and H5N1 Influenza Virus Challenge

“…If the case fatality rate of the virus remained high, an H5 pandemic could recapitulate the devastating consequences of the "Spanish" influenza pandemic of 1918, which resulted in an estimated 50 million deaths and a 10-year reduction in the average life expectancy in the United States (13). Although recent studies suggest that most 1918 (H1N1) pandemic deaths were attributed to secondary bacterial pneumonia (5), the inherent ability of the virus to replicate efficiently and cause severe acute infection of the respiratory tract was a critical underlying cause of this historic public health disaster (24,26,28,50,72,74,78,79). Thus, the 1918 influenza virus represents an ideal candidate for the study of protective immunity to a pandemic influenza virus strain.…”