scholarly journals Accurate Measurement of the Effects of All Amino-Acid Mutations on Influenza Hemagglutinin

Viruses ◽  
2016 ◽  
Vol 8 (6) ◽  
pp. 155 ◽  
Author(s):  
Michael Doud ◽  
Jesse Bloom
Keyword(s):  
Amino Acid ◽  
Influenza Hemagglutinin ◽  
Amino Acid Mutations

scholarly journals The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Bargavi Thyagarajan ◽  
Jesse D Bloom
Keyword(s):  
Amino Acid ◽  
H1n1 Influenza ◽  
Influenza Hemagglutinin ◽  
Functional Variants ◽  
Viral Hemagglutinin ◽  
Before And After ◽  
Amino Acid Mutations ◽  
And Function ◽  
Phylogenetic Models ◽  
Better Than

Influenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein's structure and function, and can be used to create a model that describes hemagglutinin's evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza's antigenic evolution.

scholarly journals Hemagglutination Inhibition (HAI) Antibody Landscapes after Vaccination with diverse H7 hemagglutinin (HA) proteins

2021 ◽  
Author(s):  
Hyesun Jang ◽  
Ted M Ross
Keyword(s):  
Amino Acid ◽  
Hemagglutination Inhibition ◽  
Lethal Dose ◽  
Antigenic Site ◽  
Glycosylation Site ◽  
Amino Acid Sequences ◽  
Serum Samples ◽  
Influenza Hemagglutinin ◽  
Amino Acid Mutations ◽  
Antigenic Profile

AbstractBackgroundA systemic evaluation of the antigenic differences of the H7 influenza hemagglutinin (HA) proteins, especially for the viruses isolated after 2016, are limited. The purpose of this study was to investigate the antigenic differences of major H7 strains with an ultimate aim to discover H7 HA proteins that can elicit protective receptor-blocking antibodies against co-circulating H7 influenza strains.MethodA panel of nine H7 influenza strains were selected from 3,633 H7 HA amino acid sequences identified over the past two decades (2000-2018). The sequences were expressed on the surface of virus like particles (VLPs) and used to vaccinate C57BL/6 mice. Serum samples were collected and tested for hemagglutination-inhibition (HAI) activity. The vaccinated mice were challenged with lethal dose of H7N9 virus, A/Anhui/1/2013.ResultsVLPs expressing the H7 HA antigens elicited broadly reactive antibodies each of the selected H7 HAs, except the A/Turkey/Italy/589/2000 (Italy/00) H7 HA. A putative glycosylation due to an A169T substitution in antigenic site B was identified as a unique antigenic profile of Italy/00. Introduction of the putative glycosylation site (H7 HA-A169T) significantly altered the antigenic profile of HA of the A/Anhui/1/2013 (H7N9) strain.ConclusionThis study identified key amino acid mutations that result in severe vaccine mismatches for future H7 epidemics. Future universal influenza vaccine candidates will need to focus on viral variants with these key mutations.

scholarly journals The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin

2014 ◽  
Author(s):  
Bargavi Thyagarajan ◽  
Jesse D. Bloom
Keyword(s):  
Amino Acid ◽  
H1n1 Influenza ◽  
Influenza Hemagglutinin ◽  
Functional Variants ◽  
Viral Hemagglutinin ◽  
Before And After ◽  
Amino Acid Mutations ◽  
And Function ◽  
Phylogenetic Models ◽  
Better Than

AbstractInfluenza is notable for its evolutionary capacity to escape immunity targeting the viral hemagglutinin. We used deep mutational scanning to examine the extent to which a high inherent mutational tolerance contributes to this antigenic evolvability. We created mutant viruses that incorporate most of the ≈ 104 amino-acid mutations to hemagglutinin from A/WSN/1933 (H1N1) influenza. After passaging these viruses in tissue culture to select for functional variants, we used deep sequencing to quantify mutation frequencies before and after selection. These data enable us to infer the preference for each amino acid at each site in hemagglutinin. These inferences are consistent with existing knowledge about the protein’s structure and function, and can be used to create a model that describes hemagglutinin’s evolution far better than existing phylogenetic models. We show that hemagglutinin has a high inherent tolerance for mutations at antigenic sites, suggesting that this is one factor contributing to influenza’s antigenic evolution.

scholarly journals Accurate measurement of the effects of all amino-acid mutations to influenza hemagglutinin

2016 ◽  
Author(s):  
Michael B. Doud ◽  
Jesse D. Bloom
Keyword(s):  
Amino Acid ◽  
Neutralizing Antibodies ◽  
Viral Evolution ◽  
Point Mutations ◽  
Helper Virus ◽  
Broadly Neutralizing Antibodies ◽  
Amino Acid Mutation ◽  
Influenza Hemagglutinin ◽  
Amino Acid Mutations ◽  
Evolutionary Paths

AbstractInfluenza genes evolve mostly via point mutations, and so knowing the effect of every amino-acid mutation provides information about evolutionary paths available to the virus. We previously used high-throughput mutagenesis and deep sequencing to estimate the effects of all mutations to an H1 influenza hemagglutinin on viral replication in cell culture (Thyagarajan and Bloom, 2014); however, these measurements suffered from sub-stantial noise. Here we describe advances that greatly improve the accuracy and reproducibility of our measurements. The largest improvements come from using a helper virus to reduce bottlenecks when generating viruses from plasmids. Our measurements confirm that antigenic sites on the globular head of hemagglutinin are highly tolerant of mutations. However, other regions – including stalk epitopes targeted by broadly neutralizing antibodies – have a limited capacity to evolve. The ability to accurately measure the effects of all influenza mutations should enhance efforts to understand and predict viral evolution.

scholarly journals Genetic Variation and Evolution of the 2019 Novel Coronavirus

2021 ◽  
pp. 1-13
Author(s):  
Salvatore Dimonte ◽  
Muhammed Babakir-Mina ◽  
Taib Hama-Soor ◽  
Salar Ali
Keyword(s):  
Amino Acid ◽  
Receptor Binding ◽  
Rapid Evolution ◽  
Single Amino Acid ◽  
Angiotensin Converting Enzyme 2 ◽  
New Type ◽  
Amino Acid Mutations ◽  
Host Infection ◽  
Human Coronaviruses ◽  
Novel Coronavirus

<b><i>Introduction:</i></b> SARS-CoV-2 is a new type of coronavirus causing a pandemic severe acute respiratory syndrome (SARS-2). Coronaviruses are very diverting genetically and mutate so often periodically. The natural selection of viral mutations may cause host infection selectivity and infectivity. <b><i>Methods:</i></b> This study was aimed to indicate the diversity between human and animal coronaviruses through finding the rate of mutation in each of the spike, nucleocapsid, envelope, and membrane proteins. <b><i>Results:</i></b> The mutation rate is abundant in all 4 structural proteins. The most number of statistically significant amino acid mutations were found in spike receptor-binding domain (RBD) which may be because it is responsible for a corresponding receptor binding in a broad range of hosts and host selectivity to infect. Among 17 previously known amino acids which are important for binding of spike to angiotensin-converting enzyme 2 (ACE2) receptor, all of them are conservative among human coronaviruses, but only 3 of them significantly are mutated in animal coronaviruses. A single amino acid aspartate-454, that causes dissociation of the RBD of the spike and ACE2, and F486 which gives the strength of binding with ACE2 remain intact in all coronaviruses. <b><i>Discussion/Conclusion:</i></b> Observations of this study provided evidence of the genetic diversity and rapid evolution of SARS-CoV-2 as well as other human and animal coronaviruses.

Detection of neutral amino acid mutations by immobilized pH gradients: The case of the Tγ variant in fetal hemoglobin Sardinia

1986 ◽  
Vol 7 (5) ◽  
pp. 213-216 ◽  
Author(s):  
Gianfranco Cossu ◽  
Mario Manca ◽  
Pier Giorgio Righetti ◽  
Elisabetta Gianazza ◽  
VÉRonique Baudin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fetal Hemoglobin ◽  
Neutral Amino Acid ◽  
Ph Gradients ◽  
Amino Acid Mutations

Structural assessment of single amino acid mutations: application to TP53 function

2006 ◽  
Vol 27 (9) ◽  
pp. 926-937 ◽  
Author(s):  
Yum L. Yip ◽  
Vincent Zoete ◽  
Holger Scheib ◽  
Olivier Michielin
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Structural Assessment ◽  
Amino Acid Mutations

Glycosylation of prions and its effects on protein conformation relevant to amino acid mutations

2000 ◽  
Vol 18 (2) ◽  
pp. 126-134 ◽  
Author(s):  
Nicky K.C Wong ◽  
David V Renouf ◽  
Sylvain Lehmann ◽  
Elizabeth F Hounsell
Keyword(s):  
Amino Acid ◽  
Protein Conformation ◽  
Amino Acid Mutations

A Combination of Amino Acid Mutations Leads to Resistance to Multiple Nucleoside Analogs in Reverse Transcriptases from HIV-1 Subtypes B and C

2021 ◽  
Author(s):  
Paul L. Boyer ◽  
Catherine A. Rehm ◽  
Michael C. Sneller ◽  
JoAnn Mican ◽  
Margaret R. Caplan ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Antiviral Drug ◽  
Nucleoside Analogs ◽  
Transcriptase Inhibitor ◽  
Reverse Transcriptases ◽  
Drug Treatments ◽  
Amino Acid Mutations ◽  
Hiv Drugs ◽  
Reverse Transcriptase Inhibitor

Resistance to anti-Human Immunodeficiency Virus (HIV) drugs has been a problem from the beginning of antiviral drug treatments. The recent expansion of combination antiretroviral therapy worldwide has led to an increase in resistance to antiretrovirals; understanding the mechanisms of resistance is increasingly important. In this study, we analyzed reverse transcriptase (RT) variants based on sequences derived from an individual who had a low-level rebound viremia while undergoing therapy with abacavir, azidothymidine (AZT or Zidovudine), and (−)-L-2′,3′-dideoxy-3′-thiacytidine (Lamivudine or 3TC). The RT had mutations at positions 64, 67, 70, 184, 219, and a threonine insertion after amino acid 69 in RT. The virus remained partially susceptible to the nucleoside reverse transcriptase inhibitor (NRTI) regimen. We show how these mutations affect the ability of NRTIs to inhibit DNA synthesis by RT. The presence of the inserted threonine reduced the susceptibility of the RT mutant to inhibition by Tenofovir.

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