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      Antiviral Mechanisms of Human Defensins

      , , *
      Journal of Molecular Biology
      Elsevier Ltd.
      CMV, cytomegalovirus, HD, human defensin, HIV, human immunodeficiency virus, HPIV, human parainfluenza virus, HSV, herpes simplex virus, IAV, influenza A virus, RSV, respiratory syncytial virus, VSV, vesicular stomatitis virus, PIV, parainfluenza virus, HAdV, human adenovirus, HPV, human papillomavirus, BKV, BK virus, LTB4, leukotriene B4, HRV, human rhinovirus, HNP, human neutrophil peptide, DC, dendritic cell, HBD, human β-defensin, PKC, protein kinase C, SBD1, sheep β-defensin 1, MBD, murine β-defensin, PBMC, peripheral blood mononuclear cell, virus, defensin, antimicrobial peptides, innate immunity

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          Defensins are an effector component of the innate immune system with broad antimicrobial activity. Humans express two types of defensins, α- and β-defensins, which have antiviral activity against both enveloped and non-enveloped viruses. The diversity of defensin-sensitive viral species reflects a multitude of antiviral mechanisms. These include direct defensin targeting of viral envelopes, glycoproteins, and capsids in addition to inhibition of viral fusion and post-entry neutralization. Binding and modulation of host cell surface receptors and disruption of intracellular signaling by defensins can also inhibit viral replication. In addition, defensins can function as chemokines to augment and alter adaptive immune responses, revealing an indirect antiviral mechanism. Nonetheless, many questions regarding the antiviral activities of defensins remain. Although significant mechanistic data are known for α-defensins, molecular details for β-defensin inhibition are mostly lacking. Importantly, the role of defensin antiviral activity in vivo has not been addressed due to the lack of a complete defensin knockout model. Overall, the antiviral activity of defensins is well established as are the variety of mechanisms by which defensins achieve this inhibition; however, additional research is needed to fully understand the role of defensins in viral pathogenesis.

          Graphical abstract


          • Defensins are active against both enveloped and non-enveloped viruses.

          • Targets include viral envelopes, glycoproteins, and capsids or host cells.

          • Multiple antiviral mechanisms have been described.

          • They can also alter immune responses to affect pathogenesis.

          • Their role in viral pathogenesis in vivo is understudied.

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          Most cited references150

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          Defensins: antimicrobial peptides of innate immunity.

          Tomas Ganz (2003)
          The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals. Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere. This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins.
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            Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis.

            Building and maintaining a homeostatic relationship between a host and its colonizing microbiota entails ongoing complex interactions between the host and the microorganisms. The mucosal immune system, including epithelial cells, plays an essential part in negotiating this equilibrium. Paneth cells (specialized cells in the epithelium of the small intestine) are an important source of antimicrobial peptides in the intestine. These cells have become the focus of investigations that explore the mechanisms of host-microorganism homeostasis in the small intestine and its collapse in the processes of infection and chronic inflammation. In this Review, we provide an overview of the intestinal microbiota and describe the cell biology of Paneth cells, emphasizing the composition of their secretions and the roles of these cells in intestinal host defence and homeostasis. We also highlight the implications of Paneth cell dysfunction in susceptibility to chronic inflammatory bowel disease.
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              Virus entry by endocytosis.

              Although viruses are simple in structure and composition, their interactions with host cells are complex. Merely to gain entry, animal viruses make use of a repertoire of cellular processes that involve hundreds of cellular proteins. Although some viruses have the capacity to penetrate into the cytosol directly through the plasma membrane, most depend on endocytic uptake, vesicular transport through the cytoplasm, and delivery to endosomes and other intracellular organelles. The internalization may involve clathrin-mediated endocytosis (CME), macropinocytosis, caveolar/lipid raft-mediated endocytosis, or a variety of other still poorly characterized mechanisms. This review focuses on the cell biology of virus entry and the different strategies and endocytic mechanisms used by animal viruses.

                Author and article information

                J Mol Biol
                J. Mol. Biol
                Journal of Molecular Biology
                Elsevier Ltd.
                2 October 2013
                13 December 2013
                2 October 2013
                : 425
                : 24
                : 4965-4980
                University of Washington School of Medicine, Box 357735, 1705 North East Pacific Street, Seattle, WA 98195, USA
                Author notes
                [* ]Corresponding author jgsmith2@ 123456uw.edu

                S.S.W. and M.E.W. contributed equally to this work.

                Copyright © 2013 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                : 3 August 2013
                : 25 September 2013
                : 26 September 2013

                Molecular biology
                cmv, cytomegalovirus,hd, human defensin,hiv, human immunodeficiency virus,hpiv, human parainfluenza virus,hsv, herpes simplex virus,iav, influenza a virus,rsv, respiratory syncytial virus,vsv, vesicular stomatitis virus,piv, parainfluenza virus,hadv, human adenovirus,hpv, human papillomavirus,bkv, bk virus,ltb4, leukotriene b4,hrv, human rhinovirus,hnp, human neutrophil peptide,dc, dendritic cell,hbd, human β-defensin,pkc, protein kinase c,sbd1, sheep β-defensin 1,mbd, murine β-defensin,pbmc, peripheral blood mononuclear cell,virus,defensin,antimicrobial peptides,innate immunity


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