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Modulation of Human β-Defensin-1 Production by Viruses


Modulation of Human β-Defensin-1 Production by Viruses

Lisa Kathleen Ryan et al. Viruses.


While initially identified as a broad-spectrum antimicrobial peptide, constitutively expressed in epithelia, human β-defensin (hBD)-1 is now recognized to have a more complex pattern of expression of its gene, DEFB1, as well as activities that extend beyond direct antimicrobial. These observations suggest a complex role for hBD-1 in the host defense against viral infections, as evidenced by its expression in cells involved in viral defense, and its gene regulation in response to viral challenge. This regulation is observed both in vitro and in vivo in humans, as well as with the murine homolog, mBD-1. While numerous reviews have summarized the existing literature on β-defensin gene expression and activity, here we provide a focused review of relevant studies on the virus-mediated regulation of hBD-1 and how this regulation can provide a crucial aspect of the innate immune defense against viral infection.

Keywords: DEFB1; antimicrobial peptide; defensin; epithelial cells; gene regulation; hBD-1; innate immunity; monocytes; plasmacytoid dendritic cells; virus.

Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.


Figure 1
Figure 1
Genetic analysis of the regulatory element of the human β-defensin-1 (hBD-1) gene, DEFB1. The flanking sequence for human β-defensin-1 was obtained from GenBank (Accession no. U50930), and analyzed for putative transcription factor binding sites by computer using MatInspector software by Genomatix (Genomatix, GmbH, Munich, Germany). It is shown in sequence format in (A) and graphically in (B). Consensus sequence for PU.1/spleen focus forming virus (SFFV) proviral integration oncogene (SPI1) binding is shown in green (A) and as light gray circles (B). Interferon regulatory factor (IRF) consensus binding sites are blue (A) and oval shaded (B); Signal transducer and activator of transcription 1 (STAT1) consensus sequences are red (A) and gray rectangles (B). Sequence of exon 1 is in italics and purple.
Figure 2
Figure 2
Transcription factors modulating hBD-1 promotor activity. Significant increase in luciferase activity (A) in A549 cells with co-transfection of the hBD-1-luciferase plasmid construct with interferon regulatory factor (IRF)-7 and PU.1 expression vectors and significant decrease in luciferase (Luc2) activity with co-transfection of an IRF-5 expression vector compared with the construct alone (p-value < 0.05). (B) Significant increase in luciferase activity over time with herpes simplex virus-1 (HSV-1) infection of OKF6/TERT cells transfected with the hBD-1 promoter/luciferase reporter construct (p-value < 0.05). Statistical analysis done with analysis of variance (ANOVA) and Tukey’s test for multiple comparisons and significant increases are indicated by one asterisk and the significant decreases are indicated by double asterisks. Expression vectors were provided by Betsy Barnes (Feinstein Institute, Manhasset, NY, USA). Transfections and analyses were carried out as described elsewhere [26].

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