Recent Advances in Molecular Biology of Human Bocavirus 1 and Its Applications

Human bocavirus 1 (HBoV1) was discovered in human nasopharyngeal specimens in 2005. It is an autonomous human parvovirus and causes acute respiratory tract infections in young children. HBoV1 infects well differentiated or polarized human airway epithelial cells in vitro. Unique among all parvoviruses, HBoV1 expresses 6 non-structural proteins, NS1, NS1-70, NS2, NS3, NS4, and NP1, and a viral non-coding RNA (BocaSR), and three structural proteins VP1, VP2, and VP3. The BocaSR is the first identified RNA polymerase III (Pol III) transcribed viral non-coding RNA in small DNA viruses. It plays an important role in regulation of viral gene expression and a direct role in viral DNA replication in the nucleus. HBoV1 genome replication in the polarized/non-dividing airway epithelial cells depends on the DNA damage and DNA repair pathways and involves error-free Y-family DNA repair DNA polymerase (Pol) η and Pol κ. Importantly, HBoV1 is a helper virus for the replication of dependoparvovirus, adeno-associated virus (AAV), in polarized human airway epithelial cells, and HBoV1 gene products support wild-type AAV replication and recombinant AAV (rAAV) production in human embryonic kidney (HEK) 293 cells. More importantly, the HBoV1 capsid is able to pseudopackage an rAAV2 or rHBoV1 genome, producing the rAAV2/HBoV1 or rHBoV1 vector. The HBoV1 capsid based rAAV vector has a high tropism for human airway epithelia. A deeper understanding in HBoV1 replication and gene expression will help find a better way to produce the rAAV vector and to increase the efficacy of gene delivery using the rAAV2/HBoV1 or rHBoV1 vector, in particular, to human airways. This review summarizes the recent advances in gene expression and replication of HBoV1, as well as the use of HBoV1 as a parvoviral vector for gene delivery.

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Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium

Scientific Reports ◽

10.1038/s41598-021-94782-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nadzeya Marozkina ◽

Laura Smith ◽

Yi Zhao ◽

Joe Zein ◽

James F. Chmiel ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Nitrogen Oxides ◽

Airway Epithelium ◽

Airflow Obstruction ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelium ◽

Human Airway Epithelial Cells

AbstractEndothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.

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Interferon-γ Inhibits STAT6 Signal Transduction and Gene Expression in Human Airway Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/rcmb.2004-0195oc ◽

2004 ◽

Vol 31 (5) ◽

pp. 573-582 ◽

Cited By ~ 51

Author(s):

Nicola M. Heller ◽

Satoshi Matsukura ◽

Steve N. Georas ◽

Mark R. Boothby ◽

Paul B. Rothman ◽

...

Keyword(s):

Gene Expression ◽

Signal Transduction ◽

Epithelial Cells ◽

Interferon Γ ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

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An analysis of glucocorticoid receptor-mediated gene expression in BEAS-2B human airway epithelial cells identifies distinct, ligand-directed, transcription profiles with implications for asthma therapeutics

British Journal of Pharmacology ◽

10.1111/bph.13014 ◽

2015 ◽

Vol 172 (5) ◽

pp. 1360-1378 ◽

Cited By ~ 17

Author(s):

T Joshi ◽

M Johnson ◽

R Newton ◽

M Giembycz

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Glucocorticoid Receptor ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Human Airway ◽

Transcription Profiles ◽

Human Airway Epithelial Cells

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AP2α is essential for MUC8 gene expression in human airway epithelial cells

Journal of Cellular Biochemistry ◽

10.1002/jcb.22655 ◽

2010 ◽

Vol 110 (6) ◽

pp. 1386-1398 ◽

Cited By ~ 5

Author(s):

Uk Yeol Moon ◽

Chang-Hoon Kim ◽

Jae Young Choi ◽

Yoon-Ju Kim ◽

Yeon Ho Choi ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

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Regulation of Thioredoxin Gene Expression by Vitamin A in Human Airway Epithelial Cells

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb.26.5.4276 ◽

2002 ◽

Vol 26 (5) ◽

pp. 627-635 ◽

Cited By ~ 8

Author(s):

Wen-Hsing Chang ◽

Sekhar P.-M. Reddy ◽

Yuan-Pu Peter Di ◽

Ken Yoneda ◽

Richart Harper ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Vitamin A ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

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Patterns of Gene Expression in Human Airway Epithelial Cells

CHEST Journal ◽

10.1378/chest.111.6_supplement.83s ◽

1997 ◽

Vol 111 (6) ◽

pp. 83S ◽

Cited By ~ 3

Author(s):

James C. Willey ◽

Mark W. Frampton ◽

Mark J. Utell ◽

Michael J. Apostolakos ◽

Erin L. Coy ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

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Expression of the endocannabinoid system in the human airway epithelial cells – Impact of sex and chronic respiratory disease status

10.1101/2020.03.01.971960 ◽

2020 ◽

Author(s):

Matthew F. Fantauzzi ◽

Jennifer A. Aguiar ◽

Benjamin J-M. Tremblay ◽

Toyoshi Yanagihara ◽

Abiram Chandiramohan ◽

...

Keyword(s):

Gene Expression ◽

Epithelial Cells ◽

Endocannabinoid System ◽

Disease Status ◽

Chronic Respiratory Disease ◽

Airway Epithelial Cells ◽

Smoke Inhalation ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

ABSTRACTRecreational and medicinal cannabis consumption in the past 12 months has been reported in 1/5th of Canadians, with greater use in males relative to females. Cannabis smoking is the dominant route of delivery in consumers, with the airway epithelium functioning as the site of first contact for inhaled phytocannabinoids. The endocannabinoid system is responsible for mediating the physiological effects of inhaled phytocannabinoids. Acute cannabis smoke inhalation can result in bronchodilation, which may have applications in chronic respiratory disease management. In contrast, chronic cannabis smoke inhalation is associated with reduced lung function and bronchitis, which challenges potential applications in the lung. The contribution of the endocannabinoid system in the airway epithelium to either beneficial or harmful physiological responses remains to be clearly defined in males and females and those with underlying chronic respiratory disease.To begin to address this knowledge gap, a curated dataset of 1090 unique human bronchial brushing gene expression profiles was created from Gene Expression Omnibus deposited microarray datasets. The dataset included 616 healthy subjects, 136 subjects with asthma, and 338 subjects with COPD. A 27-gene endocannabinoid signature was analyzed across all samples with sex and disease specific-analyses performed. Immunohistochemistry and immunoblots were performed to confirm in situ and in vitro protein expression of select genes in human airway epithelial cells.We confirm three receptors for cannabinoids, CB1, CB2, and TRPV1, are expressed at the protein level in human airway epithelial cells in situ and in vitro, justifying examining the downstream endocannabinoid pathway more extensively at the gene expression level. Sex status was associated with differential expression of 6/27 genes. In contrast, disease status was associated with differential expression of 18/27 genes in asthmatics and 22/27 genes in COPD subjects. We confirm at the protein level that TRPV1, the most differentially expressed candidate in our analyses, was up-regulated in airway epithelial cells from asthmatics relative to healthy subjects.Our data demonstrate that endocannabinoid system is expressed in human airway epithelial cells with expression impacted by disease status and minimally by sex. The data suggest that cannabis consumers may have differential physiological responses in the respiratory mucosa, which could impact both acute and chronic effects of cannabis smoke inhalation.

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