Viral-induced alternative splicing of host genes promotes influenza replication
Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here, we show that infection of human lung epithelial cells with influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. Although these splicing-regulated genes are...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2020-12-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/55500 |
id |
doaj-a84b06f84ac540deb0cf5b99ca91f58a |
---|---|
record_format |
Article |
spelling |
doaj-a84b06f84ac540deb0cf5b99ca91f58a2021-05-05T21:47:24ZengeLife Sciences Publications LtdeLife2050-084X2020-12-01910.7554/eLife.55500Viral-induced alternative splicing of host genes promotes influenza replicationMatthew G Thompson0https://orcid.org/0000-0003-3813-9254Mark Dittmar1Michael J Mallory2Prasanna Bhat3Max B Ferretti4Beatriz MA Fontoura5Sara Cherry6Kristen W Lynch7https://orcid.org/0000-0002-0120-8079Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, United States; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United StatesDepartment of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United StatesDepartment of Cell Biology, UT Southwestern Medical Center, Dallas, United StatesDepartment of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States; Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesDepartment of Cell Biology, UT Southwestern Medical Center, Dallas, United StatesBiochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, United States; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States; Department of Pathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United StatesBiochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, United States; Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United StatesViral infection induces the expression of numerous host genes that impact the outcome of infection. Here, we show that infection of human lung epithelial cells with influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. Although these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, in several cases, specific inhibition of the IAV-induced splicing pattern also attenuates viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein required for efficient splicing of the IAV M transcript in nuclear speckles. Finally, we find an increase in hnRNP K in nuclear speckles upon IAV infection, which may alter accessibility of hnRNP K for host transcripts thereby leading to a program of host splicing changes that promote IAV replication.https://elifesciences.org/articles/55500virus infectionalternative splicinghnRNP Kinfluenza |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Matthew G Thompson Mark Dittmar Michael J Mallory Prasanna Bhat Max B Ferretti Beatriz MA Fontoura Sara Cherry Kristen W Lynch |
spellingShingle |
Matthew G Thompson Mark Dittmar Michael J Mallory Prasanna Bhat Max B Ferretti Beatriz MA Fontoura Sara Cherry Kristen W Lynch Viral-induced alternative splicing of host genes promotes influenza replication eLife virus infection alternative splicing hnRNP K influenza |
author_facet |
Matthew G Thompson Mark Dittmar Michael J Mallory Prasanna Bhat Max B Ferretti Beatriz MA Fontoura Sara Cherry Kristen W Lynch |
author_sort |
Matthew G Thompson |
title |
Viral-induced alternative splicing of host genes promotes influenza replication |
title_short |
Viral-induced alternative splicing of host genes promotes influenza replication |
title_full |
Viral-induced alternative splicing of host genes promotes influenza replication |
title_fullStr |
Viral-induced alternative splicing of host genes promotes influenza replication |
title_full_unstemmed |
Viral-induced alternative splicing of host genes promotes influenza replication |
title_sort |
viral-induced alternative splicing of host genes promotes influenza replication |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2020-12-01 |
description |
Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here, we show that infection of human lung epithelial cells with influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. Although these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, in several cases, specific inhibition of the IAV-induced splicing pattern also attenuates viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein required for efficient splicing of the IAV M transcript in nuclear speckles. Finally, we find an increase in hnRNP K in nuclear speckles upon IAV infection, which may alter accessibility of hnRNP K for host transcripts thereby leading to a program of host splicing changes that promote IAV replication. |
topic |
virus infection alternative splicing hnRNP K influenza |
url |
https://elifesciences.org/articles/55500 |
work_keys_str_mv |
AT matthewgthompson viralinducedalternativesplicingofhostgenespromotesinfluenzareplication AT markdittmar viralinducedalternativesplicingofhostgenespromotesinfluenzareplication AT michaeljmallory viralinducedalternativesplicingofhostgenespromotesinfluenzareplication AT prasannabhat viralinducedalternativesplicingofhostgenespromotesinfluenzareplication AT maxbferretti viralinducedalternativesplicingofhostgenespromotesinfluenzareplication AT beatrizmafontoura viralinducedalternativesplicingofhostgenespromotesinfluenzareplication AT saracherry viralinducedalternativesplicingofhostgenespromotesinfluenzareplication AT kristenwlynch viralinducedalternativesplicingofhostgenespromotesinfluenzareplication |
_version_ |
1721457902817902592 |