An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization
Abstract Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2023-10-01
|
Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-023-41308-4 |
_version_ | 1797558670803861504 |
---|---|
author | Carol M. Sheppard Daniel H. Goldhill Olivia C. Swann Ecco Staller Rebecca Penn Olivia K. Platt Ksenia Sukhova Laury Baillon Rebecca Frise Thomas P. Peacock Ervin Fodor Wendy S. Barclay |
author_facet | Carol M. Sheppard Daniel H. Goldhill Olivia C. Swann Ecco Staller Rebecca Penn Olivia K. Platt Ksenia Sukhova Laury Baillon Rebecca Frise Thomas P. Peacock Ervin Fodor Wendy S. Barclay |
author_sort | Carol M. Sheppard |
collection | DOAJ |
description | Abstract Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza A virus in these edited cells and unexpectedly, after 2 passages, we observe robust viral growth. We find two mutations in different subunits of the influenza polymerase that enable the mutant virus to use a novel host factor, ANP32E, an alternative family member, which is unable to support the wild type polymerase. Both mutations reside in the symmetric dimer interface between two polymerase complexes and reduce polymerase dimerization. These mutations have previously been identified as adapting influenza viruses to mice. Indeed, the evolved virus gains the ability to use suboptimal mouse ANP32 proteins and becomes more virulent in mice. We identify further mutations in the symmetric dimer interface which we predict allow influenza to adapt to use suboptimal ANP32 proteins through a similar mechanism. Overall, our results suggest a balance between asymmetric and symmetric dimers of influenza virus polymerase that is influenced by the interaction between polymerase and ANP32 host proteins. |
first_indexed | 2024-03-10T17:34:29Z |
format | Article |
id | doaj.art-9ea86ca4471f48e0947e131249f06d09 |
institution | Directory Open Access Journal |
issn | 2041-1723 |
language | English |
last_indexed | 2024-03-10T17:34:29Z |
publishDate | 2023-10-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
spelling | doaj.art-9ea86ca4471f48e0947e131249f06d092023-11-20T09:54:04ZengNature PortfolioNature Communications2041-17232023-10-0114111610.1038/s41467-023-41308-4An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerizationCarol M. Sheppard0Daniel H. Goldhill1Olivia C. Swann2Ecco Staller3Rebecca Penn4Olivia K. Platt5Ksenia Sukhova6Laury Baillon7Rebecca Frise8Thomas P. Peacock9Ervin Fodor10Wendy S. Barclay11Department of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonSir William Dunn School of Pathology, University of OxfordDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonDepartment of Infectious Disease, Imperial College LondonSir William Dunn School of Pathology, University of OxfordDepartment of Infectious Disease, Imperial College LondonAbstract Human ANP32A and ANP32B are essential but redundant host factors for influenza virus genome replication. While most influenza viruses cannot replicate in edited human cells lacking both ANP32A and ANP32B, some strains exhibit limited growth. Here, we experimentally evolve such an influenza A virus in these edited cells and unexpectedly, after 2 passages, we observe robust viral growth. We find two mutations in different subunits of the influenza polymerase that enable the mutant virus to use a novel host factor, ANP32E, an alternative family member, which is unable to support the wild type polymerase. Both mutations reside in the symmetric dimer interface between two polymerase complexes and reduce polymerase dimerization. These mutations have previously been identified as adapting influenza viruses to mice. Indeed, the evolved virus gains the ability to use suboptimal mouse ANP32 proteins and becomes more virulent in mice. We identify further mutations in the symmetric dimer interface which we predict allow influenza to adapt to use suboptimal ANP32 proteins through a similar mechanism. Overall, our results suggest a balance between asymmetric and symmetric dimers of influenza virus polymerase that is influenced by the interaction between polymerase and ANP32 host proteins.https://doi.org/10.1038/s41467-023-41308-4 |
spellingShingle | Carol M. Sheppard Daniel H. Goldhill Olivia C. Swann Ecco Staller Rebecca Penn Olivia K. Platt Ksenia Sukhova Laury Baillon Rebecca Frise Thomas P. Peacock Ervin Fodor Wendy S. Barclay An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization Nature Communications |
title | An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization |
title_full | An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization |
title_fullStr | An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization |
title_full_unstemmed | An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization |
title_short | An Influenza A virus can evolve to use human ANP32E through altering polymerase dimerization |
title_sort | influenza a virus can evolve to use human anp32e through altering polymerase dimerization |
url | https://doi.org/10.1038/s41467-023-41308-4 |
work_keys_str_mv | AT carolmsheppard aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT danielhgoldhill aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT oliviacswann aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT eccostaller aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT rebeccapenn aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT oliviakplatt aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT kseniasukhova aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT laurybaillon aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT rebeccafrise aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT thomasppeacock aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT ervinfodor aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT wendysbarclay aninfluenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT carolmsheppard influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT danielhgoldhill influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT oliviacswann influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT eccostaller influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT rebeccapenn influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT oliviakplatt influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT kseniasukhova influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT laurybaillon influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT rebeccafrise influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT thomasppeacock influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT ervinfodor influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization AT wendysbarclay influenzaaviruscanevolvetousehumananp32ethroughalteringpolymerasedimerization |