scholarly journals Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing

2021 ◽  
Author(s):  
Yiquan Wang ◽  
Ruipeng Lei ◽  
Armita Nourmohammad ◽  
Nicholas C. Wu
Keyword(s):  
Fitness Landscape ◽  
H3n2 Virus ◽  
Effective Vaccine ◽  
Human Influenza ◽  
Net Charge ◽  
Antigenic Region ◽  
Immune Pressure ◽  
Antigenic Evolution ◽  
Charge Balancing ◽  
Influenza H3n2

As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has emerged as an effective vaccine target recently, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply deep mutational scanning to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region can be predicted by charge states and pairwise epistasis. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a predictive model of influenza evolution.

scholarly journals Antigenic evolution of human influenza H3N2 neuraminidase is constrained by charge balancing

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yiquan Wang ◽  
Ruipeng Lei ◽  
Armita Nourmohammad ◽  
Nicholas C Wu
Keyword(s):  
Fitness Landscape ◽  
H3n2 Virus ◽  
Effective Vaccine ◽  
Net Charge ◽  
Antigenic Region ◽  
Immune Pressure ◽  
Antigenic Evolution ◽  
Combinatorial Mutagenesis ◽  
Charge Balancing ◽  
Generation Sequencing

As one of the main influenza antigens, neuraminidase (NA) in H3N2 virus has evolved extensively for more than 50 years due to continuous immune pressure. While NA has recently emerged as an effective vaccine target, biophysical constraints on the antigenic evolution of NA remain largely elusive. Here, we apply combinatorial mutagenesis and next-generation sequencing to characterize the local fitness landscape in an antigenic region of NA in six different human H3N2 strains that were isolated around 10 years apart. The local fitness landscape correlates well among strains and the pairwise epistasis is highly conserved. Our analysis further demonstrates that local net charge governs the pairwise epistasis in this antigenic region. In addition, we show that residue coevolution in this antigenic region is correlated with the pairwise epistasis between charge states. Overall, this study demonstrates the importance of quantifying epistasis and the underlying biophysical constraint for building a model of influenza evolution.

Surveillance of human influenza A(H3N2) virus from 1999 to 2009 in southern Italy

2013 ◽  
Vol 142 (5) ◽  
pp. 933-939 ◽  
Author(s):  
A. DE DONNO ◽  
A. IDOLO ◽  
M. QUATTROCCHI ◽  
A. ZIZZA ◽  
G. GABUTTI ◽  
...  
Keyword(s):  
New York ◽  
Influenza A ◽  
Southern Italy ◽  
Influenza Viruses ◽  
H3n2 Virus ◽  
Human Influenza ◽  
Ha Gene ◽  
Previous Season ◽  
Virus Strains ◽  
Influenza H3n2

SUMMARYThe aim of this study was to evaluate the presence of influenza virus co-infections in humans and changes in the genetic variability of A(H3N2) virus strains in southern Italy from 1999 to 2009. A partial sequence of the haemagglutinin (HA) gene by human influenza H3N2 strains identified in oropharyngeal swabs from patients with influenza-like illness was analysed by DNA sequencing and a phylogenetic analysis was performed. During the seasons 1999–2000, 2002–2003, 2004–2005 and 2008–2009, the influenza viruses circulating belonged to subtype H3N2. However, A(H1N1) subtype virus and B type were respectively prevalent during the 2000–2001, 2006–2007, 2007–2008 and 2001–2002, 2003–2004, 2005–2006 seasons. The HA sequences appeared to be closely related to the sequence of the influenza A vaccine strain. Only the 2002–2003 season was characterized by co-circulation of two viral lineages: A/New York/55/01(H3N2)-like virus of the previous season and A/Fujian/411/02(H3N2)-like virus, a new H3 variant. In this study, over the decade analysed, no significant change was seen in the sequences of the HA gene of H3 viruses isolated.

scholarly journals Major antigenic site B of human influenza H3N2 viruses has an evolving local fitness landscape

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicholas C. Wu ◽  
Jakub Otwinowski ◽  
Andrew J. Thompson ◽  
Corwin M. Nycholat ◽  
Armita Nourmohammad ◽  
...  
Keyword(s):  
Fitness Landscape ◽  
Antigenic Site ◽  
Human Influenza ◽  
Influenza H3n2

Analysis of the beta-propiolactone sensitivity and optimization of inactivation methods for human influenza H3N2 virus

2016 ◽  
Vol 235 ◽  
pp. 105-111 ◽  
Author(s):  
Yutaka Sasaki ◽  
Naoto Yoshino ◽  
Shigehiro Sato ◽  
Yasushi Muraki
Keyword(s):  
H3n2 Virus ◽  
Human Influenza ◽  
Influenza H3n2

scholarly journals Genetic evolution of the neuraminidase of influenza A (H3N2) viruses from 1968 to 2009 and its correspondence to haemagglutinin evolution

2012 ◽  
Vol 93 (9) ◽  
pp. 1996-2007 ◽  
Author(s):  
Kim B. Westgeest ◽  
Miranda de Graaf ◽  
Mathieu Fourment ◽  
Theo M. Bestebroer ◽  
Ruud van Beek ◽  
...  
Keyword(s):  
Humoral Immunity ◽  
Influenza A ◽  
Phylogenetic Trees ◽  
Influenza Viruses ◽  
Genetic Maps ◽  
Genetic Evolution ◽  
Human Influenza ◽  
Nucleotide Level ◽  
Antigenic Evolution ◽  
Positively Selected Sites

Each year, influenza viruses cause epidemics by evading pre-existing humoral immunity through mutations in the major glycoproteins: the haemagglutinin (HA) and the neuraminidase (NA). In 2004, the antigenic evolution of HA of human influenza A (H3N2) viruses was mapped (Smith et al., Science 305, 371–376, 2004) from its introduction in humans in 1968 until 2003. The current study focused on the genetic evolution of NA and compared it with HA using the dataset of Smith and colleagues, updated to the epidemic of the 2009/2010 season. Phylogenetic trees and genetic maps were constructed to visualize the genetic evolution of NA and HA. The results revealed multiple reassortment events over the years. Overall rates of evolutionary change were lower for NA than for HA1 at the nucleotide level. Selection pressures were estimated, revealing an abundance of negatively selected sites and sparse positively selected sites. The differences found between the evolution of NA and HA1 warrant further analysis of the evolution of NA at the phenotypic level, as has been done previously for HA.

scholarly journals Vaccination against Human Influenza A/H3N2 Virus Prevents the Induction of Heterosubtypic Immunity against Lethal Infection with Avian Influenza A/H5N1 Virus

PLoS ONE ◽  
2009 ◽  
Vol 4 (5) ◽  
pp. e5538 ◽  
Author(s):  
Rogier Bodewes ◽  
Joost H. C. M. Kreijtz ◽  
Chantal Baas ◽  
Martina M. Geelhoed-Mieras ◽  
Gerrie de Mutsert ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
H5n1 Virus ◽  
H3n2 Virus ◽  
Human Influenza ◽  
Lethal Infection ◽  
Heterosubtypic Immunity

Molecular and antigenic evolution of human influenza A/H3N2 viruses in Quebec, Canada, 2009–2011

2012 ◽  
Vol 53 (1) ◽  
pp. 88-92 ◽  
Author(s):  
Julie Ann ◽  
Jesse Papenburg ◽  
Xavier Bouhy ◽  
Chantal Rhéaume ◽  
Marie-Ève Hamelin ◽  
...  
Keyword(s):  
Influenza A ◽  
Human Influenza ◽  
Antigenic Evolution

scholarly journals Mutational networks of escape from transmitted HIV-1 infection

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243391
Author(s):  
Elma H. Akand ◽  
Stephen J. Maher ◽  
John M. Murray
Keyword(s):  
Immune Response ◽  
Effective Vaccine ◽  
Subtype C ◽  
Hub And Spoke ◽  
Binding Domains ◽  
Immune Pressure ◽  
Subtype B ◽  
Combined Operations ◽  
Founder Virus ◽  
Coreceptor Binding

Human immunodeficiency virus (HIV) is subject to immune selective pressure soon after it establishes infection at the founder stage. As an individual progresses from the founder to chronic stage of infection, immune pressure forces a history of mutations that are embedded in envelope sequences. Determining this pathway of coevolving mutations can assist in understanding what is different with the founder virus and the essential pathways it takes to maintain infection. We have combined operations research and bioinformatics methods to extract key networks of mutations that differentiate founder and chronic stages for 156 subtype B and 107 subtype C envelope (gp160) sequences. The chronic networks for both subtypes revealed strikingly different hub-and-spoke topologies compared to the less structured transmission networks. This suggests that the hub nodes are impacted by the immune response and the resulting loss of fitness is compensated by mutations at the spoke positions. The major hubs in the chronic C network occur at positions 12, 137 (within the N136 glycan), and 822, and at position 306 for subtype B. While both founder networks had a more heterogeneous connected network structure, interestingly founder B subnetworks around positions 640 and 837 preferentially contained CD4 and coreceptor binding domains. Finally, we observed a differential effect of glycosylation between founder and chronic subtype B where the latter had mutational pathways significantly driven by N-glycosylation. Our study provides insights into the mutational pathways HIV takes to evade the immune response, and presents features more likely to establish founder infection, valuable for effective vaccine design.

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