Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype.
Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases. Adaptive mutations arise among the thousands of variants generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly permissive and less permissive environment. Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner. We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype.
Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France; Institut Pasteur, International Group for Data Analysis, Paris, France.
Antonio V
AV
Bordería
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ofer
O
Isakov
Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France.
Gonzalo
G
Moratorio
Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France; Institut Pasteur, International Group for Data Analysis, Paris, France; Centre for Mathematical Sciences, Lund University, Lund, Sweden.
Rasmus
R
Henningsson
Institut Pasteur, Lymphocyte Cell Biology Unit, CNRS URA 1960, Paris, France.
Sonia
S
Agüera-González
Division of Infectious Diseases, Pennsylvania State College of Medicine, Hershey, Pennsylvania, United States of America.
Lindsey
L
Organtini
Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France.
Nina F
NF
Gnädig
Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France.
Hervé
H
Blanc
Institut Pasteur, Lymphocyte Cell Biology Unit, CNRS URA 1960, Paris, France.
Andrés
A
Alcover
Division of Infectious Diseases, Pennsylvania State College of Medicine, Hershey, Pennsylvania, United States of America.
Susan
S
Hafenstein
Institut Pasteur, International Group for Data Analysis, Paris, France; Centre for Mathematical Sciences, Lund University, Lund, Sweden.
Magnus
M
Fontes
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Noam
N
Shomron
Institut Pasteur, Viral Populations and Pathogenesis Unit, CNRS UMR 3569, Paris, France.
Marco
M
Vignuzzi
D000220:Adaptation, Biological / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D029822:Enterovirus B, Human / Q000235:genetics*; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D014779:Virus Replication / Q000235:genetics*