Abstract
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.
Highlights
Human papillomavirus (HPV) remains the most common sexually transmitted infection within the human population and it is estimated that over 80% of all sexually active individuals will be infected at one point in their lifetimes [1]
We found that the presence of serum during the PsV+RTD-1 pre-incubation steps resulted in a failure of RTD-1 to inhibit PsV infection (Figure 1C), suggesting that competing serum proteins can interfere with the initial interaction between RTD-1 and the virus capsid
Within this study we have expanded the list of defensins that act against HPV to include θ-defensins by characterizing how the prototype θ-defensin, RTD-1, inhibits HPV16
Summary
Human papillomavirus (HPV) remains the most common sexually transmitted infection within the human population and it is estimated that over 80% of all sexually active individuals will be infected at one point in their lifetimes [1]. Persistent infection with a high-risk HPV (hrHPV) genotype is causally associated with the development of both anogenital and oropharyngeal cancers [2, 3]. The number of hrHPV-positive head and neck cancers occurring in men has seen a dramatic increase, underscoring that infection with hrHPV is a health burden on all sexually active individuals [5, 6]. In both cases, the primary genotype associated with either cervical cancer (CC) or oropharyngeal squamous cell carcinoma (OPSCC) was HPV16, which is found in >50% of CC and >90% OPSCC [7, 8]. There is a continuous need to develop and test novel methods that may be used to prevent the transmission of hrHPV that can work alongside
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