Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering
Persistent infection with high-risk human papillomavirus (hrHPV) genotypes results in a large number of anogenital and head and neck cancers worldwide. Although prophylactic vaccination coverage has improved, there remains a need to develop methods that inhibit viral transmission toward preventing t...
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.561843/full |
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doaj-95f0f794df68498dbee0a0c227fdac122020-11-25T03:42:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.561843561843Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid ClusteringJoseph G. Skeate0Wouter H. Segerink1Mauricio D. Garcia2Daniel J. Fernandez3Ruben Prins4Kim P. Lühen5Féline O. Voss6Diane M. Da Silva7Diane M. Da Silva8W. Martin Kast9W. Martin Kast10W. Martin Kast11Department of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesNorris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United StatesDepartment of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesNorris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United StatesDepartment of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesDepartment of Molecular Microbiology & Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesNorris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United StatesDepartment of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United StatesPersistent infection with high-risk human papillomavirus (hrHPV) genotypes results in a large number of anogenital and head and neck cancers worldwide. Although prophylactic vaccination coverage has improved, there remains a need to develop methods that inhibit viral transmission toward preventing the spread of HPV-driven disease. Defensins are a class of innate immune effector peptides that function to protect hosts from infection by pathogens such as viruses and bacteria. Previous work utilizing α and β defensins from humans has demonstrated that the α-defensin HD5 is effective at inhibiting the most common high-risk genotype, HPV16. A third class of defensin that has yet to be explored are θ-defensins: small, 18-amino acid cyclic peptides found in old-world monkeys whose unique structure makes them both highly cationic and resistant to degradation. Here we show that the prototype θ-defensin, rhesus theta defensin 1, inhibits hrHPV infection through a mechanism involving capsid clustering that inhibits virions from binding to cell surface receptor complexes.https://www.frontiersin.org/article/10.3389/fimmu.2020.561843/fullhuman papillomavirusalpha-defensinstheta-defensinsinfectioninnate-immunologysexually transmitted infection (STI) |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Joseph G. Skeate Wouter H. Segerink Mauricio D. Garcia Daniel J. Fernandez Ruben Prins Kim P. Lühen Féline O. Voss Diane M. Da Silva Diane M. Da Silva W. Martin Kast W. Martin Kast W. Martin Kast |
| spellingShingle |
Joseph G. Skeate Wouter H. Segerink Mauricio D. Garcia Daniel J. Fernandez Ruben Prins Kim P. Lühen Féline O. Voss Diane M. Da Silva Diane M. Da Silva W. Martin Kast W. Martin Kast W. Martin Kast Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering Frontiers in Immunology human papillomavirus alpha-defensins theta-defensins infection innate-immunology sexually transmitted infection (STI) |
| author_facet |
Joseph G. Skeate Wouter H. Segerink Mauricio D. Garcia Daniel J. Fernandez Ruben Prins Kim P. Lühen Féline O. Voss Diane M. Da Silva Diane M. Da Silva W. Martin Kast W. Martin Kast W. Martin Kast |
| author_sort |
Joseph G. Skeate |
| title |
Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering |
| title_short |
Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering |
| title_full |
Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering |
| title_fullStr |
Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering |
| title_full_unstemmed |
Theta-Defensins Inhibit High-Risk Human Papillomavirus Infection Through Charge-Driven Capsid Clustering |
| title_sort |
theta-defensins inhibit high-risk human papillomavirus infection through charge-driven capsid clustering |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Immunology |
| issn |
1664-3224 |
| publishDate |
2020-09-01 |
| description |
Persistent infection with high-risk human papillomavirus (hrHPV) genotypes results in a large number of anogenital and head and neck cancers worldwide. Although prophylactic vaccination coverage has improved, there remains a need to develop methods that inhibit viral transmission toward preventing the spread of HPV-driven disease. Defensins are a class of innate immune effector peptides that function to protect hosts from infection by pathogens such as viruses and bacteria. Previous work utilizing α and β defensins from humans has demonstrated that the α-defensin HD5 is effective at inhibiting the most common high-risk genotype, HPV16. A third class of defensin that has yet to be explored are θ-defensins: small, 18-amino acid cyclic peptides found in old-world monkeys whose unique structure makes them both highly cationic and resistant to degradation. Here we show that the prototype θ-defensin, rhesus theta defensin 1, inhibits hrHPV infection through a mechanism involving capsid clustering that inhibits virions from binding to cell surface receptor complexes. |
| topic |
human papillomavirus alpha-defensins theta-defensins infection innate-immunology sexually transmitted infection (STI) |
| url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.561843/full |
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