Journal article
Cellular Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Mediates Nuclear Import of Human Bocavirus 1 NP1 Protein and Modulates Viral Capsid Protein Expression
Journal of virology, Vol.94(2), e01444-19
01/06/2020
DOI: 10.1128/JVI.01444-19
PMCID: PMC6955249
PMID: 31666379
Abstract
Human bocavirus 1 (HBoV1), which belongs to the genus Bocaparvovirus of the Parvoviridae family, causes acute respiratory tract infections in young children. In vitro, HBoV1 infects polarized primary human airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI). HBoV1 encodes a small nonstructural protein, nuclear protein 1 (NP1), that plays an essential role in the maturation of capsid protein (VP)-encoding mRNAs and viral DNA replication. In this study, we determined the broad interactome of NP1 using the proximity-dependent biotin identification (BioID) assay combined with mass spectrometry (MS). We confirmed that two host mRNA processing factors, DEAH-box helicase 15 (DHX15) and cleavage and polyadenylation specificity factor 6 (CPSF6; also known as CFIm68), a subunit of the cleavage factor Im complex (CFIm), interact with HBoV1 NP1 independently of any DNA or mRNAs. Knockdown of CPSF6 significantly decreased the expression of capsid protein but not that of DHX15. We further demonstrated that NP1 directly interacts with CPSF6 in vitro and colocalizes within the virus replication centers. Importantly, we revealed a novel role of CPSF6 in the nuclear import of NP1, in addition to the critical role of CPSF6 in NP1-facilitated maturation of VP-encoding mRNAs. Thus, our study suggests that CPSF6 interacts with NP1 to escort NP1 imported into the nucleus for its function in the modulation of viral mRNA processing and viral DNA replication.
Details
- Title: Subtitle
- Cellular Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Mediates Nuclear Import of Human Bocavirus 1 NP1 Protein and Modulates Viral Capsid Protein Expression
- Creators
- Xiaomei Wang - University of Kansas Medical CenterPeng Xu - University of Kansas Medical CenterFang Cheng - University of Kansas Medical CenterYi Li - Wuhan UniversityZekun Wang - University of Kansas Medical CenterSiyuan Hao - University of Kansas Medical CenterJianke Wang - University of Kansas Medical CenterKang Ning - University of Kansas Medical CenterSafder S Ganaie - University of Kansas Medical CenterJohn F Engelhardt - University of IowaZiying Yan - University of IowaJianming Qiu - University of Kansas Medical Center
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.94(2), e01444-19
- DOI
- 10.1128/JVI.01444-19
- PMID
- 31666379
- PMCID
- PMC6955249
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- P30 GM122731 / NIGMS NIH HHS R21 AI139572 / NIAID NIH HHS P30 ES005605 / NIEHS NIH HHS R01 AI070723 / NIAID NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 01/06/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284346402771
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