Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009

ABSTRACT Influenza A viruses (IAVs) can cause zoonotic infections with pandemic potential when most of the human population is immunologically naive. After a pandemic, IAVs evolve to become seasonal in the human host by acquiring adaptive mutations. We have previously reported that the interferon (I...

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Autores principales:	Isabel Pagani, Andrea Di Pietro, Alexandra Oteiza, Michela Ghitti, Nadir Mechti, Nadia Naffakh, Elisa Vicenzi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	influenza A virus TRIM22 evolution nucleoprotein restriction Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/859e81a9b890458684b2c5c2d67ccc01
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spelling	oai:doaj.org-article:859e81a9b890458684b2c5c2d67ccc012021-11-15T15:22:13ZMutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 200910.1128/mSphere.00110-182379-5042https://doaj.org/article/859e81a9b890458684b2c5c2d67ccc012018-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00110-18https://doaj.org/toc/2379-5042ABSTRACT Influenza A viruses (IAVs) can cause zoonotic infections with pandemic potential when most of the human population is immunologically naive. After a pandemic, IAVs evolve to become seasonal in the human host by acquiring adaptive mutations. We have previously reported that the interferon (IFN)-inducible tripartite motif 22 (TRIM22) protein restricts the replication of seasonal IAVs by direct interaction with the viral nucleoprotein (NP), leading to its polyubiquitination and proteasomal degradation. Here we show that, in contrast to seasonal H1N1 IAVs, the 2009 pandemic H1N1 strain as well as H1N1 strains from the 1930s are resistant to TRIM22 restriction. We demonstrate that arginine-to-lysine substitutions conferring an increased sensitivity to TRIM22-dependent ubiquitination accumulated progressively in the NP of seasonal influenza A (H1N1) viruses between 1918 and 2009. Our findings suggest that during long-term circulation and evolution of IAVs in humans, adaptive mutations are favored at the expense of an increased sensitivity to some components of the innate immune response. IMPORTANCE We have uncovered that long-term circulation of seasonal influenza A viruses (IAV) in the human population resulted in the progressive acquisition of increased sensitivity to a component of the innate immune response: the type I interferon-inducible TRIM22 protein, which acts as a restriction factor by inducing the polyubiquitination of the IAV nucleoprotein (NP). We show that four arginine residues present in the NP of the 1918 H1N1 pandemic strain and early postpandemic strains were progressively substituted for by lysines between 1918 and 2009, rendering NP more susceptible to TRIM22-mediated ubiquitination. Our observations suggest that during long-term evolution of IAVs in humans, variants endowed with increased susceptibility to TRIM22 restriction emerge, highlighting the complexity of selection pressures acting on the NP.Isabel PaganiAndrea Di PietroAlexandra OteizaMichela GhittiNadir MechtiNadia NaffakhElisa VicenziAmerican Society for Microbiologyarticleinfluenza A virusTRIM22evolutionnucleoproteinrestrictionMicrobiologyQR1-502ENmSphere, Vol 3, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	influenza A virus TRIM22 evolution nucleoprotein restriction Microbiology QR1-502
spellingShingle	influenza A virus TRIM22 evolution nucleoprotein restriction Microbiology QR1-502 Isabel Pagani Andrea Di Pietro Alexandra Oteiza Michela Ghitti Nadir Mechti Nadia Naffakh Elisa Vicenzi Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009
description	ABSTRACT Influenza A viruses (IAVs) can cause zoonotic infections with pandemic potential when most of the human population is immunologically naive. After a pandemic, IAVs evolve to become seasonal in the human host by acquiring adaptive mutations. We have previously reported that the interferon (IFN)-inducible tripartite motif 22 (TRIM22) protein restricts the replication of seasonal IAVs by direct interaction with the viral nucleoprotein (NP), leading to its polyubiquitination and proteasomal degradation. Here we show that, in contrast to seasonal H1N1 IAVs, the 2009 pandemic H1N1 strain as well as H1N1 strains from the 1930s are resistant to TRIM22 restriction. We demonstrate that arginine-to-lysine substitutions conferring an increased sensitivity to TRIM22-dependent ubiquitination accumulated progressively in the NP of seasonal influenza A (H1N1) viruses between 1918 and 2009. Our findings suggest that during long-term circulation and evolution of IAVs in humans, adaptive mutations are favored at the expense of an increased sensitivity to some components of the innate immune response. IMPORTANCE We have uncovered that long-term circulation of seasonal influenza A viruses (IAV) in the human population resulted in the progressive acquisition of increased sensitivity to a component of the innate immune response: the type I interferon-inducible TRIM22 protein, which acts as a restriction factor by inducing the polyubiquitination of the IAV nucleoprotein (NP). We show that four arginine residues present in the NP of the 1918 H1N1 pandemic strain and early postpandemic strains were progressively substituted for by lysines between 1918 and 2009, rendering NP more susceptible to TRIM22-mediated ubiquitination. Our observations suggest that during long-term evolution of IAVs in humans, variants endowed with increased susceptibility to TRIM22 restriction emerge, highlighting the complexity of selection pressures acting on the NP.
format	article
author	Isabel Pagani Andrea Di Pietro Alexandra Oteiza Michela Ghitti Nadir Mechti Nadia Naffakh Elisa Vicenzi
author_facet	Isabel Pagani Andrea Di Pietro Alexandra Oteiza Michela Ghitti Nadir Mechti Nadia Naffakh Elisa Vicenzi
author_sort	Isabel Pagani
title	Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009
title_short	Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009
title_full	Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009
title_fullStr	Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009
title_full_unstemmed	Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009
title_sort	mutations conferring increased sensitivity to tripartite motif 22 restriction accumulated progressively in the nucleoprotein of seasonal influenza a (h1n1) viruses between 1918 and 2009
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/859e81a9b890458684b2c5c2d67ccc01
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Mutations Conferring Increased Sensitivity to Tripartite Motif 22 Restriction Accumulated Progressively in the Nucleoprotein of Seasonal Influenza A (H1N1) Viruses between 1918 and 2009

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