Influenza A virus encodes two segments (7 and 8) that produce mRNAs that can be spliced. We have investigated if naturally occurring sequence polymorphisms in the influenza A virus family affects splicing of these viral mRNAs, as that could potentially alter the NS1/NS2- and/or M1/M2-protein ratios. We compared splicing efficiency of segment 7 and 8 mRNAs of A/Brevig Mission/1918/1 (H1N1) and A...

Of the unexplained characteristics of the 1918-19 influenza pandemic, the extreme mortality rate among young adults (W-shaped mortality curve) is the foremost. Lack of a coherent explanation of this and other epidemiologic and clinical manifestations of the pandemic contributes to uncertainty in preparing for future pandemics. Contemporaneous records suggest that immunopathologic responses were...

The 1918 "Spanish flu" was the fastest spreading and most deadly influenza pandemic in recorded history. Hypotheses of its origin have been based on a limited collection of case and outbreak reports from before its recognized European emergence in the summer of 1918. These anecdotal accounts, however, remain insufficient for determining the early diffusion and impact of the pandemic virus. Usin...

This essay proposes that the ecologic association shown between the 20th century coronary heart disease epidemic and the 1918 influenza pandemic could shed light on the mechanism associated with the high lethality of the latter. It suggests that an autoimmune interference at the apoB-LDL interface could explain both hypercholesterolemia and inflammation (through interference with the cellular m...

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 huma...

To understand the reported cross-reactivity of the 2009 H1N1 and the 1918 H1N1 pandemic viruses we docked the crystal structure of 2D1, an antibody derived from a survivor of the 1918 pandemic, to the structures of hemaglutinin (HA) of the 2009 strain and seasonal H1 vaccine strains. Our studies revealed that 2D1 binds to the 2009 HA at antigenic site 'Sa', with stabilizing contacts, similar to...

The effect of the 1918 influenza pandemic on other diseases is a neglected topic in historical epidemiology. This paper takes up the hypothesis that the influenza pandemic affected the long-term decline of tuberculosis through selective mortality, such that many people with tuberculosis were killed in 1918, depressing subsequent tuberculosis mortality and transmission. Regularly collected vital...

Michael Stoker Sir Michael Stoker, a pioneer of virology and the cell biology of cancer cells, died on 13 August at the age of 95. Viruses have always been useful tools for probing the workings of cells, and Michael exploited tumor-causing viruses to gain a better understanding of oncogenic mechanisms at the dawn of the molecular biology of animal cells. During a long career, Michael not only m...

Howard Schachman, renowned physical chemist and protein chemist, professor at the University of California, Berkeley, extraordinary teacher, and a lifetime fighter for civil liberties, died on August 5 in Oakland California at age 97 from complications of pneumonia. Schachman’s active career spanned fundamental work on virus structure, the development of the analytical ultracentrifuge and its u...

The Meuse-Argonne offensive, a decisive battle during the First World War, is the largest frontline commitment in American military history involving 1.2 million U.S. troops. With over 26,000 deaths among American soldiers, the offensive is considered "America's deadliest battle". The Meuse-Argonne offensive coincided with the highly fatal second wave of the influenza pandemic in 1918. In Europ...