Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 ‘Spanish’ Influenza Pandemic Virus

Reis, Mario dos; Hay, Alan J.; Goldstein, Richard A.

doi:10.1007/s00239-009-9282-x

Cited by 35 publications

(37 citation statements)

References 56 publications

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“…Nearly all these motifs consist of CpGs in an A/U context. These motifs are present at fairly high levels in the 1918 H1N1 influenza virus strain, which is thought to have been of recent avian origin (15). However, the number of motifs decreased as this viral strain continued to evolve in the human population (21).…”

Section: Motifs Containing Cpg Dinucleotides Distinguish Avian and Mamentioning

confidence: 98%

Oligonucleotide Motifs That Disappear during the Evolution of Influenza Virus in Humans Increase Alpha Interferon Secretion by Plasmacytoid Dendritic Cells

Jiménez-Baranda

Greenbaum

Manches

et al. 2011

J Virol

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Section: Motifs Containing Cpg Dinucleotides Distinguish Avian and Mamentioning

confidence: 98%

Oligonucleotide Motifs That Disappear during the Evolution of Influenza Virus in Humans Increase Alpha Interferon Secretion by Plasmacytoid Dendritic Cells

Jiménez-Baranda

Greenbaum

Manches

et al. 2011

J Virol

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“…The two most highly expressed influenza virus proteins are NP and M1 (49), and epitopes in these proteins are major targets of CD8 ϩ T cells (3,4,8,9). The NP and M1 proteins in contemporary human H3N2 influenza viruses have circulated in humans since at least 1918 (50,51). For both genes, this unbroken lineage consists of H1N1 viruses from 1918 to 1957, H2N2 viruses from 1957 to 1968, and H3N2 viruses from 1968 to the present.…”

Section: Parallel Human and Swine Influenza Virus Lineages Reveal Selmentioning

confidence: 99%

“…This human influenza virus lineage is closely paralleled by a swine influenza virus lineage descended from the common ancestor of the virus that caused concurrent pandemics in humans and swine in 1918 (50,52). NP and M1 of this lineage have circulated exclusively in swine since 1918 (50,52).…”

Section: Parallel Human and Swine Influenza Virus Lineages Reveal Selmentioning

confidence: 99%

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Positive Selection in CD8⁺T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

Machkovech

Bedford

Suchard³

et al. 2015

J Virol

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Numerous experimental studies have demonstrated that CD8؉ T cells contribute to immunity against influenza by limiting viral replication. It is therefore surprising that rigorous statistical tests have failed to find evidence of positive selection in the epitopes targeted by CD8؉ T cells. Here we use a novel computational approach to test for selection in CD8 ؉ T-cell epitopes. We define all epitopes in the nucleoprotein (NP) and matrix protein (M1) with experimentally identified human CD8 ؉ T-cell responses and then compare the evolution of these epitopes in parallel lineages of human and swine influenza viruses that have been diverging since roughly 1918. We find a significant enrichment of substitutions that alter human CD8؉ T-cell epitopes in NP of human versus swine influenza virus, consistent with the idea that these epitopes are under positive selection. Furthermore, we show that epitope-altering substitutions in human influenza virus NP are enriched on the trunk versus the branches of the phylogenetic tree, indicating that viruses that acquire these mutations have a selective advantage. However, even in human influenza virus NP, sites in T-cell epitopes evolve more slowly than do nonepitope sites, presumably because these epitopes are under stronger inherent functional constraint. Overall, our work demonstrates that there is clear selection from CD8 ؉ T cells in human influenza virus NP and illustrates how comparative analyses of viral lineages from different hosts can identify positive selection that is otherwise obscured by strong functional constraint. IMPORTANCEThere is a strong interest in correlates of anti-influenza immunity that are protective against diverse virus strains. CD8 ؉ T cells provide such broad immunity, since they target conserved viral proteins. An important question is whether T-cell immunity is sufficiently strong to drive influenza virus evolution. Although many studies have shown that T cells limit viral replication in animal models and are associated with decreased symptoms in humans, no studies have proven with statistical significance that influenza virus evolves under positive selection to escape T cells. Here we use comparisons of human and swine influenza viruses to rigorously demonstrate that human influenza virus evolves under pressure to fix mutations in the nucleoprotein that promote escape from T cells. We further show that viruses with these mutations have a selective advantage since they are preferentially located on the "trunk" of the phylogenetic tree. Overall, our results show that CD8 ؉ T cells targeting nucleoprotein play an important role in shaping influenza virus evolution. Both arms of the adaptive immune system help control influenza virus replication: antibodies neutralize virus (1) and direct the clearance of infected cells (2), while CD8 ϩ T cells kill infected cells that display viral peptides on their major histocompatibility complex (MHC) class I molecules (3, 4). While antibodies against the viral surface protein hemagglutinin (HA) provide ...

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“…We use the estimates to calculate v k , g k and v þ k here. The classical lineage of human influenza probably originated from a host shift from an avian to a mammal reservoir in the early-twentieth century [12]. We calculate v The probability that the site is fixed for I, time t after the environment shift is Pr (B)…”

Section: The Non-synonymous Rate During Adaptive Evolutionmentioning

confidence: 99%

How to calculate the non-synonymous to synonymous rate ratio of protein-coding genes under the Fisher–Wright mutation–selection framework

Reis

2015

Biol. Lett.

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First principles of population genetics are used to obtain formulae relating the non-synonymous to synonymous substitution rate ratio to the selection coefficients acting at codon sites in protein-coding genes. Two theoretical cases are discussed and two examples from real data (a chloroplast gene and a virus polymerase) are given. The formulae give much insight into the dynamics of non-synonymous substitutions and may inform the development of methods to detect adaptive evolution.

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Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 ‘Spanish’ Influenza Pandemic Virus

Abstract: Nonhomogeneous Markov models of nucleotide substitution have received scant attention.

Cited by 35 publications

References 56 publications

Oligonucleotide Motifs That Disappear during the Evolution of Influenza Virus in Humans Increase Alpha Interferon Secretion by Plasmacytoid Dendritic Cells

Oligonucleotide Motifs That Disappear during the Evolution of Influenza Virus in Humans Increase Alpha Interferon Secretion by Plasmacytoid Dendritic Cells

Positive Selection in CD8⁺T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

How to calculate the non-synonymous to synonymous rate ratio of protein-coding genes under the Fisher–Wright mutation–selection framework

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Using Non-Homogeneous Models of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918 ‘Spanish’ Influenza Pandemic Virus

Abstract: Nonhomogeneous Markov models of nucleotide substitution have received scant attention.

Cited by 35 publications

References 56 publications

Oligonucleotide Motifs That Disappear during the Evolution of Influenza Virus in Humans Increase Alpha Interferon Secretion by Plasmacytoid Dendritic Cells

Oligonucleotide Motifs That Disappear during the Evolution of Influenza Virus in Humans Increase Alpha Interferon Secretion by Plasmacytoid Dendritic Cells

Positive Selection in CD8+T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages

How to calculate the non-synonymous to synonymous rate ratio of protein-coding genes under the Fisher–Wright mutation–selection framework

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Positive Selection in CD8⁺T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages