Adaptive evolution of PB1 from influenza A(H1N1)pdm09 virus towards an enhanced fitness

Santos, Luís A.; Almeida, Filipe; Gíria, Marta; Trigueiro-Louro, João; Rebelo-de-Andrade, Helena

http://hdl.handle.net/10400.18/8567

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Autores

Santos, Luís A.

Almeida, Filipe

Gíria, Marta

Trigueiro-Louro, João

Rebelo-de-Andrade, Helena

Resumo(s)

PB1 influenza virus retain traces of interspecies transmission and adaptation. Previous phylogenetic analyses highlighted mutations L298I, R386K and I517V in PB1 to have putatively ameliorated the A(H1N1)pdm09 adaptation to the human host. This study aimed to evaluate the reversal of these mutations and infer the role of these residues in the virus overall fitness and adaptation. We generate PB1-mutated viruses introducing I298L, K386R and V517I mutations in PB1 and evaluate their phenotypic impact on viral growth and on antigen yield. We observed a decrease in viral growth accompanied by a reduction in hemagglutination titer and neuraminidase activity, in comparison with wt. Our data indicate that the adaptive evolution occurred in the PB1 leads to an improved overall viral fitness; and such biologic advantaged has the potential to be applied to the optimization of influenza vaccine seed prototypes.

Highlights: PB1 protein of influenza virus retain traces of interspecies transmission and adaptation; The modulation of PB1 sites 298, 386 and 517 have a significant impact on viral growth and antigen yield; Exploring the structure-function relation of PB1 sites to optimize the viral genomic composition of vaccine seed prototypes; Our work is useful for structure-based vaccine prototype design and optimization for the A(H1N1)pdm09 virus.

Palavras-chave

Influenza Influenza A Virus Vaccine Prototypes Protein Adaptation PB1 Co-segregation Viral Fitness Infecções Respiratórias Resistência aos Antimicrobianos