Journal article
Human Parvovirus Infection of Human Airway Epithelia Induces Pyroptotic Cell Death by Inhibiting Apoptosis
Journal of virology, Vol.91(24), e01533-17
12/15/2017
DOI: 10.1128/JVI.01533-17
PMCID: PMC5709578
PMID: 29021400
Abstract
Human bocavirus 1 (HBoV1) is a human parvovirus that causes acute respiratory tract infections in young children. In this study, we confirmed that, when polarized/well-differentiated human airway epithelia are infected with HBoV1
, they develop damage characterized by barrier function disruption and cell hypotrophy. Cell death mechanism analyses indicated that the infection induced pyroptotic cell death characterized by caspase-1 activation. Unlike infections with other parvoviruses, HBoV1 infection did not activate the apoptotic or necroptotic cell death pathway. When the NLRP3-ASC-caspase-1 inflammasome-induced pathway was inhibited by short hairpin RNA (shRNA), HBoV1-induced cell death dropped significantly; thus, NLRP3 mediated by ASC appears to be the pattern recognition receptor driving HBoV1 infection-induced pyroptosis. HBoV1 infection induced steady increases in the expression of interleukin 1α (IL-1α) and IL-18. HBoV1 infection was also associated with the marked expression of the antiapoptotic genes
and
When the expression of
and/or
was inhibited by shRNA, the infected cells underwent apoptosis rather than pyroptosis, as indicated by increased cleaved caspase-3 levels and the absence of caspase-1.
and/or
gene inhibition also significantly reduced HBoV1 replication. Thus, HBoV1 infection of human airway epithelial cells activates antiapoptotic proteins that suppress apoptosis and promote pyroptosis. This response may have evolved to confer a replicative advantage, thus allowing HBoV1 to establish a persistent airway epithelial infection. This is the first report of pyroptosis in airway epithelia infected by a respiratory virus.
Microbial infection of immune cells often induces pyroptosis, which is mediated by a cytosolic protein complex called the inflammasome that senses microbial pathogens and then activates the proinflammatory cytokines IL-1 and IL-18. While virus-infected airway epithelia often activate NLRP3 inflammasomes, studies to date suggest that these viruses kill the airway epithelial cells via the apoptotic or necrotic pathway; involvement of the pyroptosis pathway has not been reported previously. Here, we show for the first time that virus infection of human airway epithelia can also induce pyroptosis. Human bocavirus 1 (HBoV1), a human parvovirus, causes lower respiratory tract infections in young children. This study indicates that HBoV1 kills airway epithelial cells by activating genes that suppress apoptosis and thereby promote pyroptosis. This strategy appears to promote HBoV1 replication and may have evolved to allow HBoV1 to establish persistent infection of human airway epithelia.
Details
- Title: Subtitle
- Human Parvovirus Infection of Human Airway Epithelia Induces Pyroptotic Cell Death by Inhibiting Apoptosis
- Creators
- Xuefeng Deng - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USAWei Zou - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USAMin Xiong - Department of Pediatrics and Department of Biomedical and Health Informatics, Children's Mercy Hospital and University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USAZekun Wang - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USAJohn F Engelhardt - Center for Gene Therapy, University of Iowa, Iowa City, Iowa, USAShui Qing Ye - Department of Pediatrics and Department of Biomedical and Health Informatics, Children's Mercy Hospital and University of Missouri Kansas City School of Medicine, Kansas City, Missouri, USAZiying Yan - Center for Gene Therapy, University of Iowa, Iowa City, Iowa, USAJianming Qiu - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA jqiu@kumc.edu
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.91(24), e01533-17
- Publisher
- United States
- DOI
- 10.1128/JVI.01533-17
- PMID
- 29021400
- PMCID
- PMC5709578
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- R21 AI105543 / NIAID NIH HHS R01 AI070723 / NIAID NIH HHS R56 AI070723 / NIAID NIH HHS R21 AI112803 / NIAID NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 12/15/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025414802771
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