Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus

Abstract

The source, timing, and geographical origin of the 1918-1920 pandemic influenza A virus have remained tenaciously obscure for nearly a century, as have the reasons for its unusual severity among young adults. Here, we reconstruct the origins of the pandemic virus and the classic swine influenza and (postpandemic) seasonal H1N1 lineages using a host-specific molecular clock approach that is demonstrably more accurate than previous methods. Our results suggest that the 1918 pandemic virus originated shortly before 1918 when a human H1 virus, which we infer emerged before ∼1907, acquired avian N1 neuraminidase and internal protein genes. We find that the resulting pandemic virus jumped directly to swine but was likely displaced in humans by ∼1922 by a reassortant with an antigenically distinct H1 HA. Hence, although the swine lineage was a direct descendent of the pandemic virus, the post-1918 seasonal H1N1 lineage evidently was not, at least for HA. These findings help resolve several seemingly disparate observations from 20th century influenza epidemiology, seroarcheology, and immunology. The phylogenetic results, combined with these other lines of evidence, suggest that the high mortality in 1918 among adults aged ∼20 to ∼40 y may have been due primarily to their childhood exposure to a doubly heterosubtypic putative H3N8 virus, which we estimate circulated from ∼1889-1900. All other age groups (except immunologically naive infants) were likely partially protected by childhood exposure to N1 and/or H1-related antigens. Similar processes may underlie age-specific mortality differences between seasonal H1N1 vs. H3N2 and human H5N1 vs. H7N9 infections.phylogeny | cohort immunity | pathogenicity | virulence | reassortment

Hemagglutinin Stalk- and Neuraminidase-Specific Monoclonal Antibodies Protect against Lethal H10N8 Influenza Virus Infection in Mice

“…Importantly, we found strong reactivity to potential pandemic viruses like H3N8, which caused a severe outbreak in harbor seals in New England in 2012, as well as against the N8 NA of the newly emerging, highly pathogenic H5N8 viruses (26,30,31,36,37). The H3N8 subtype is also important, since it was speculated to be the cause of a human pandemic in 1889 (38). This suggests that the isolated MAbs could be used as therapeutics against emerging viruses of the H10 or N8 subtype and that H10N8 vaccines could have broad efficacy against those viruses as well.…”

Identification of Patient Zero in Static and Temporal Networks: Robustness and Limitations

“…Epidemiologists detect the epidemic source or the patient-zero either by analysing the temporal genetic evolution of virus strains [8][9][10], which can be time-demanding or try to do a contact backtracking [11] from the available observed data. However, in cases where the information on the times of contact is unknown or incomplete or the infection is asymptomatic or subclinical the backtracking method is no longer adequate.…”

Differential Recognition of Influenza A Viruses by M158–66Epitope-Specific CD8+T Cells Is Determined by Extraepitopic Amino Acid Residues

“…Other IAV subtypes circulate in animal reservoirs, like aquatic birds and pigs (4), but can occasionally cross the species barrier into the human population (5). Genetic reassortment between animal and human IAVs has resulted in the emergence of pandemic strains in the last century (6)(7)(8)(9).…”