Please use this identifier to cite or link to this item: https://doi.org/10.1186/1743-422X-7-297
Title: All that glitters is not gold - Founder effects complicate associations of flu mutations to disease severity
Authors: Lee, R.T
Santos, C.L
Maria De Paiva, T
Cui, L
Sirota, F.L
Eisenhaber, F 
Maurer-Stroh, S 
Keywords: article
controlled study
disease association
disease severity
epidemiological data
fatality
founder effect
futurology
gene
gene mutation
genome
HA D239G gene
HA D239N gene
HA Q310 H gene
influenza
nonhuman
nucleotide sequence
PB2 K340N gene
phenotype
phylogenetic tree
sample
virus genome
chemical structure
founder effect
genetics
human
influenza
Influenza virus A H1N1
missense mutation
pathogenicity
pathology
phylogeny
prevalence
protein tertiary structure
virology
virulence
hemagglutinin fusogenic peptide, influenza virus
virulence factor
virus hemagglutinin
virus RNA
Founder Effect
Hemagglutinins, Viral
Humans
Influenza A Virus, H1N1 Subtype
Influenza, Human
Models, Molecular
Mutation, Missense
Phylogeny
Prevalence
Protein Structure, Tertiary
RNA, Viral
Virulence
Virulence Factors
Issue Date: 2010
Citation: Lee, R.T, Santos, C.L, Maria De Paiva, T, Cui, L, Sirota, F.L, Eisenhaber, F, Maurer-Stroh, S (2010). All that glitters is not gold - Founder effects complicate associations of flu mutations to disease severity. Virology Journal 7 : 297. ScholarBank@NUS Repository. https://doi.org/10.1186/1743-422X-7-297
Abstract: Background: The recent 2009 (H1N1) influenza A pandemic saw a rapid spread of the virus to essentially all parts of the world. In the course of its evolution, the virus acquired many mutations, some of which have been investigated in the context of increased severity due to high occurrences in fatal cases. For example, statements such as: "42.9% of individuals who died from laboratory-confirmed cases of the pandemic (H1N1) were infected with the hemagglutinin (HA) Q310 H mutant virus." give the impression that HA-Q310 H would be highly dangerous or important, while careful consideration of all available data suggests that this is unlikely to be the case. Results. We compare the mutations HA-Q310 H, PB2-K340N, HA-D239N and HA-D239G using whole genome phylogenetic trees, structural modeling in their 3 D context and complete epidemiological data from sequences to clinical outcomes. HA-Q310 H and PB2-K340N appear as isolated subtrees in the phylogenetic analysis pointing to founder effects which is consistent with their clustered temporal appearance as well as the lack of an immediate structural basis that could explain a change of phenotypes. Considering the prevailing viral genomic background, shared origin of samples (all from the city of Sao Paulo) and narrow temporal window (all death case samples within 1 month), it becomes clear that HA-Q310 H was actually a generally common mutation in the region at that time which could readily explain its increased occurrence among the few analyzed fatal cases without requiring necessarily an association with severity. In further support of this, we highlight 3 mild cases with the HA-Q310 H mutation. Conclusions. We argue that claims of severity of any current and future flu mutation need to be critically considered in the light of phylogenetic, structural and detailed epidemiological data to distinguish increased occurrence due to possible founder effects rather than real phenotypic changes. © 2010 Leeet al licensee BioMed Central Ltd.
Source Title: Virology Journal
URI: https://scholarbank.nus.edu.sg/handle/10635/174180
ISSN: 1743422X
DOI: 10.1186/1743-422X-7-297
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