Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells
Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both...
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description | Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection. |
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In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1009908</identifier><identifier>PMID: 34529742</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Airway (Medicine) ; Assembly ; Biology and Life Sciences ; Biosynthesis ; Cholesterol ; Coenzyme A ; Cytopathology ; Cytoplasm ; Cytotoxicity ; Development and progression ; Epidemics ; Gene expression ; Health aspects ; Host-virus relationships ; Hydroxymethylglutaryl-CoA reductase ; Infections ; Lipid rafts ; Lipids ; Measles ; Medicine and Health Sciences ; Parainfluenza ; Parainfluenza viruses ; Physiological aspects ; Progeny ; Protein synthesis ; Proteins ; Reductases ; Respiratory syncytial virus ; Respiratory tract ; RNA virus infections ; Synthesis ; Ubiquitination ; Viral infections ; Virions ; Viruses</subject><ispartof>PLoS pathogens, 2021-09, Vol.17 (9), p.e1009908-e1009908</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Kurebayashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Kurebayashi et al 2021 Kurebayashi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c704t-c12e28f925b9bcdfe5407ca3d8d25834dcebcbd30f0eefde0bd68fc8dfd593793</citedby><cites>FETCH-LOGICAL-c704t-c12e28f925b9bcdfe5407ca3d8d25834dcebcbd30f0eefde0bd68fc8dfd593793</cites><orcidid>0000-0001-9261-7726 ; 0000-0002-3318-0808 ; 0000-0001-6612-694X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445407/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445407/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids></links><search><contributor>Kawaoka, Yoshihiro</contributor><creatorcontrib>Kurebayashi, Yuki</creatorcontrib><creatorcontrib>Bajimaya, Shringkhala</creatorcontrib><creatorcontrib>Watanabe, Masahiro</creatorcontrib><creatorcontrib>Lim, Nicholas</creatorcontrib><creatorcontrib>Lutz, Michael</creatorcontrib><creatorcontrib>Dunagan, Megan</creatorcontrib><creatorcontrib>Takimoto, Toru</creatorcontrib><title>Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells</title><title>PLoS pathogens</title><description>Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection.</description><subject>Airway (Medicine)</subject><subject>Assembly</subject><subject>Biology and Life Sciences</subject><subject>Biosynthesis</subject><subject>Cholesterol</subject><subject>Coenzyme A</subject><subject>Cytopathology</subject><subject>Cytoplasm</subject><subject>Cytotoxicity</subject><subject>Development and progression</subject><subject>Epidemics</subject><subject>Gene expression</subject><subject>Health aspects</subject><subject>Host-virus relationships</subject><subject>Hydroxymethylglutaryl-CoA reductase</subject><subject>Infections</subject><subject>Lipid rafts</subject><subject>Lipids</subject><subject>Measles</subject><subject>Medicine and Health Sciences</subject><subject>Parainfluenza</subject><subject>Parainfluenza viruses</subject><subject>Physiological aspects</subject><subject>Progeny</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Reductases</subject><subject>Respiratory syncytial virus</subject><subject>Respiratory tract</subject><subject>RNA virus infections</subject><subject>Synthesis</subject><subject>Ubiquitination</subject><subject>Viral 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parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells</title><author>Kurebayashi, Yuki ; Bajimaya, Shringkhala ; Watanabe, Masahiro ; Lim, Nicholas ; Lutz, Michael ; Dunagan, Megan ; Takimoto, Toru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c704t-c12e28f925b9bcdfe5407ca3d8d25834dcebcbd30f0eefde0bd68fc8dfd593793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Airway (Medicine)</topic><topic>Assembly</topic><topic>Biology and Life Sciences</topic><topic>Biosynthesis</topic><topic>Cholesterol</topic><topic>Coenzyme A</topic><topic>Cytopathology</topic><topic>Cytoplasm</topic><topic>Cytotoxicity</topic><topic>Development and progression</topic><topic>Epidemics</topic><topic>Gene expression</topic><topic>Health aspects</topic><topic>Host-virus relationships</topic><topic>Hydroxymethylglutaryl-CoA reductase</topic><topic>Infections</topic><topic>Lipid rafts</topic><topic>Lipids</topic><topic>Measles</topic><topic>Medicine and Health Sciences</topic><topic>Parainfluenza</topic><topic>Parainfluenza viruses</topic><topic>Physiological aspects</topic><topic>Progeny</topic><topic>Protein synthesis</topic><topic>Proteins</topic><topic>Reductases</topic><topic>Respiratory syncytial virus</topic><topic>Respiratory tract</topic><topic>RNA virus infections</topic><topic>Synthesis</topic><topic>Ubiquitination</topic><topic>Viral infections</topic><topic>Virions</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kurebayashi, Yuki</creatorcontrib><creatorcontrib>Bajimaya, Shringkhala</creatorcontrib><creatorcontrib>Watanabe, Masahiro</creatorcontrib><creatorcontrib>Lim, Nicholas</creatorcontrib><creatorcontrib>Lutz, Michael</creatorcontrib><creatorcontrib>Dunagan, Megan</creatorcontrib><creatorcontrib>Takimoto, 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pathogens</jtitle><date>2021-09-16</date><risdate>2021</risdate><volume>17</volume><issue>9</issue><spage>e1009908</spage><epage>e1009908</epage><pages>e1009908-e1009908</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34529742</pmid><doi>10.1371/journal.ppat.1009908</doi><orcidid>https://orcid.org/0000-0001-9261-7726</orcidid><orcidid>https://orcid.org/0000-0002-3318-0808</orcidid><orcidid>https://orcid.org/0000-0001-6612-694X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Airway (Medicine) Assembly Biology and Life Sciences Biosynthesis Cholesterol Coenzyme A Cytopathology Cytoplasm Cytotoxicity Development and progression Epidemics Gene expression Health aspects Host-virus relationships Hydroxymethylglutaryl-CoA reductase Infections Lipid rafts Lipids Measles Medicine and Health Sciences Parainfluenza Parainfluenza viruses Physiological aspects Progeny Protein synthesis Proteins Reductases Respiratory syncytial virus Respiratory tract RNA virus infections Synthesis Ubiquitination Viral infections Virions Viruses |
title | Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells |
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