Journal article
Identification and Functional Analysis of Novel Nonstructural Proteins of Human Bocavirus 1
Journal of virology, Vol.89(19), pp.10097-10109
10/2015
DOI: 10.1128/JVI.01374-15
PMCID: PMC4577888
PMID: 26223640
Abstract
Human bocavirus 1 (HBoV1) is a single-stranded DNA parvovirus that causes lower respiratory tract infections in young children worldwide. In this study, we identified novel splice acceptor and donor sites, namely, A1' and D1', in the large nonstructural protein (NS1)-encoding region of the HBoV1 precursor mRNA. The novel small NS proteins (NS2, NS3, and NS4) were confirmed to be expressed following transfection of an HBoV1 infectious proviral plasmid and viral infection of polarized human airway epithelium cultured at an air-liquid interface (HAE-ALI). We constructed mutant pIHBoV1 infectious plasmids which harbor silent mutations (sm) smA1' and smD1' at the A1' and D1' splice sites, respectively. The mutant infectious plasmids maintained production of HBoV1 progeny virions at levels less than five times lower than that of the wild-type plasmid. Importantly, the smA1' mutant virus that does not express NS3 and NS4 replicated in HAE-ALI as effectively as the wild-type virus; however, the smD1' mutant virus that does not express NS2 and NS4 underwent an abortive infection in HAE-ALI. Thus, our study identified three novel NS proteins, NS2, NS3, and NS4, and suggests an important function of the NS2 protein in HBoV1 replication in HAE-ALI.
Human bocavirus 1 infection causes respiratory diseases, including acute wheezing in infants, of which life-threatening cases have been reported. In vitro, human bocavirus 1 infects polarized human bronchial airway epithelium cultured at an air-liquid interface that mimics the environment of human lower respiratory airways. Viral nonstructural proteins are often important for virus replication and pathogenesis in infected tissues or cells. In this report, we identified three new nonstructural proteins of human bocavirus 1 that are expressed during infection of polarized human bronchial airway epithelium. Among them, we proved that one nonstructural protein is critical to the replication of the virus in polarized human bronchial airway epithelium. The creation of nonreplicating infectious HBoV1 mutants may have particular utility in vaccine development for this virus.
Details
- Title: Subtitle
- Identification and Functional Analysis of Novel Nonstructural Proteins of Human Bocavirus 1
- Creators
- Weiran Shen - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USAXuefeng 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, USAFang Cheng - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USAJohn F Engelhardt - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USAZiying Yan - Department of Anatomy and Cell Biology, 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.89(19), pp.10097-10109
- Publisher
- United States
- DOI
- 10.1128/JVI.01374-15
- PMID
- 26223640
- PMCID
- PMC4577888
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- R01 HL108902 / NHLBI NIH HHS AI070723 / NIAID NIH HHS R56 AI070723 / NIAID NIH HHS R21 AI112803 / NIAID NIH HHS AI105543 / NIAID NIH HHS P30 GM103326 / NIGMS NIH HHS R21 AI105543 / NIAID NIH HHS AI112803 / NIAID NIH HHS R01 AI070723 / NIAID NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 10/2015
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025454802771
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