Journal article
Parvovirus Expresses a Small Noncoding RNA That Plays an Essential Role in Virus Replication
Journal of virology, Vol.91(8), e02375-16
04/15/2017
DOI: 10.1128/JVI.02375-16
PMCID: PMC5375684
PMID: 28122984
Abstract
Human bocavirus 1 (HBoV1) belongs to the species
of the genus
of the
family. HBoV1 causes acute respiratory tract infections in young children and has a selective tropism for the apical surface of well-differentiated human airway epithelia (HAE). In this study, we identified an additional HBoV1 gene, bocavirus-transcribed small noncoding RNA (BocaSR), within the 3' noncoding region (nucleotides [nt] 5199 to 5338) of the viral genome of positive sense. BocaSR is transcribed by RNA polymerase III (Pol III) from an intragenic promoter at levels similar to that of the capsid protein-coding mRNA and is essential for replication of the viral DNA in both transfected HEK293 and infected HAE cells. Mechanistically, we showed that BocaSR regulates the expression of HBoV1-encoded nonstructural proteins NS1, NS2, NS3, and NP1 but not NS4. BocaSR is similar to the adenovirus-associated type I (VAI) RNA in terms of both nucleotide sequence and secondary structure but differs from it in that its regulation of viral protein expression is independent of RNA-activated protein kinase (PKR) regulation. Notably, BocaSR accumulates in the viral DNA replication centers within the nucleus and likely plays a direct role in replication of the viral DNA. Our findings reveal BocaSR to be a novel viral noncoding RNA that coordinates the expression of viral proteins and regulates replication of viral DNA within the nucleus. Thus, BocaSR may be a target for antiviral therapies for HBoV and may also have utility in the production of recombinant HBoV vectors.
Human bocavirus 1 (HBoV1) is pathogenic to humans, causing acute respiratory tract infections in young children. In this study, we identified a novel HBoV1 gene that lies in the 3' noncoding region of the viral positive-sense genome and is transcribed by RNA polymerase III into a noncoding RNA of 140 nt. This bocavirus-transcribed small RNA (BocaSR) diverges from both adenovirus-associated (VA) RNAs and Epstein-Barr virus-encoded small RNAs (EBERs) with respect to RNA sequence, representing a third species of this kind of Pol III-dependent viral noncoding RNA and the first noncoding RNA identified in autonomous parvoviruses. Unlike the VA RNAs, BocaSR localizes to the viral DNA replication centers of the nucleus and is essential for expression of viral nonstructural proteins independent of RNA-activated protein kinase R and replication of HBoV1 genomes. The identification of BocaSR and its role in virus DNA replication reveals potential avenues for developing antiviral therapies.
Details
- Title: Subtitle
- Parvovirus Expresses a Small Noncoding RNA That Plays an Essential Role in Virus Replication
- Creators
- Zekun Wang - Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USAWeiran Shen - 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, USAXuefeng Deng - 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.91(8), e02375-16
- Publisher
- United States
- DOI
- 10.1128/JVI.02375-16
- PMID
- 28122984
- PMCID
- PMC5375684
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- R56 AI070723 / NIAID NIH HHS R21 AI112803 / NIAID NIH HHS P30 GM103326 / NIGMS NIH HHS R21 AI105543 / NIAID NIH HHS R01 AI070723 / NIAID NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS
- Language
- English
- Date published
- 04/15/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025304002771
Metrics
15 Record Views