Spanish Influenza Virus Research Articles

Influenza as a bioweapon

Influenza as a bioweapon

The haemagglutinin gene, but not the neuraminidase gene, of 'Spanish flu' was a recombinant.

Published analyses of the sequences of three genes from the 1918 Spanish influenza virus have cast doubt on the theory that it came from birds immediately before the pandemic. They showed that the virus was of the H1N1 subtype lineage but more closely related to mammal-infecting strains than any known bird-infecting strain. They provided no evidence that the virus originated by gene reassortment nor that the virus was the direct ancestor of the two lineages of H1N1 viruses currently found in mammals; one that mostly infects human beings, the other pigs. The unusual virulence of the virus and why it produced a pandemic have remained unsolved. We have reanalysed the sequences of the three 1918 genes and found conflicting patterns of relatedness in all three. Various tests showed that the patterns in its haemagglutinin (HA) gene were produced by true recombination between two different parental HA H1 subtype genes, but that the conflicting patterns in its neuraminidase and non-structural-nuclear export proteins genes resulted from selection. The recombination event that produced the 1918 HA gene probably coincided with the start of the pandemic, and may have triggered it.

Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus

The Spanish influenza pandemic of 1918-1919 caused acute illness in 25-30% of the world's population and resulted in the death of 40 million people. The complete genomic sequence of the 1918 influenza virus will be deduced using fixed and frozen tissues of 1918 influenza victims. Sequence and phylogenetic analyses of the complete 1918 haemagglutinin (HA) and neuraminidase (NA) genes show them to be the most avian-like of mammalian sequences and support the hypothesis that the pandemic virus contained surface protein-encoding genes derived from an avian influenza strain and that the 1918 virus is very similar to the common ancestor of human and classical swine H1N1 influenza strains. Neither the 1918 HA genes nor the NA genes possessed mutations that are known to increase tissue tropicity, which accounts for the virulence of other influenza strains such as A/WSN/33 or fowl plague viruses. The complete sequence of the nonstructural (NS) gene segment of the 1918 virus was deduced and tested for the hypothesis that the enhanced virulence in 1918 could have been due to type I interferon inhibition by the NS1 protein. The results from these experiments were inconclusive. Sequence analysis of the 1918 pandemic influenza virus is allowing us to test hypotheses as to the origin and virulence of this strain. This information should help to elucidate how pandemic influenza strains emerge and what genetic features contribute to their virulence.

Prevention and control of influenza

I nfluenza-vires infections remain among the most frequent causes of medically attended respiratory disease, primarily beause these diverse, rapidly mutating (figure), and unpredictable viruses produce multiple illnesses throughout the lifetime of an individual. In 1971, Alexander Langmuir wrote, Since 1957, influenza epidemics have continued to be a major, senous,~ and intractable health problem, as frustrating to an action and control orientated epidemiologist as poliomyelitis has been gratifying. This quotation is more poignant today, for we have made little progress in the prevention and control of influenza, despite significant progress in understanding the structure, replication, immunology, and epidemiology of influenza, and the availability of effective inactivated influenza vaccines and antiviral drags. Each of the three pandemics this century (1918, 1957, 1968) was associated with high rates of morbidity, social disruption, and high economic costs. The 1918 pandemic claimed more than 20 million victims worldwide in less than 1 year, more than deaths from war or famine in an equivalent period. Even though a partial genetic sequence has been rescued recently from preserved tissue, we still do not understand why the 1918 pandemic was associated with an unusually high case-fatality rate in young healthy adults. However, with the expected future publication of the entire gene sequence of the Spanish influenza virus of 1918, this deadly organism could be reconstructed with modem techniques of nucleic-acid synthesis and gene rescue. Furthermore, technical advances in molecular genetics now make it possible to engineer influenza viruses with made-to-order genomes, and may transform influenza viruses into a potential bioterrorism threat. Another natural pandemic of influenza is likely to strike, although we cannot predict when it will happen or how serious it will be. This concern is based on observations from past centuries, and on current knowledge about the avian and swine reservoirs for influenza viruses and the mechanisms for emergence of novel pandemic strains. This lesson has been driven home by recent human infections with avian influenza viruses in Hong Kong. Increases in global travel and world population during the past century will probably contribute to more rapid spread of pandemic influenza during the next millennium than in the past. Inactivated vaccines now available were first developed over 50 years ago, and are now generally recommended for people at increased risk of complications. The adamantanes (amantadine, rimantadine) have been approved for prevention and treatment of influenza A infections in some countries for decades, but have not had widespread use, primarily because of concerns about side-effects and Influenza A(H3N2) Haemagglutinin