Delineation of Interfaces on Human Alpha-Defensins Critical for Human Adenovirus and Human Papillomavirus Inhibition

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Human α-defensins are an important component of the innate immune response and provide an initial block against a broad number of infectious agents, including viruses and bacteria. Characteristics of α-defensins that are necessary for their anti-bacterial activity have been identified, but our understanding of determinants required for activity against non-enveloped viruses is limited. In this work, we utilized alanine scan mutagenesis to systematically and comprehensively investigate the role of hydrophobic and charged residues of two α-defensins in binding to and/or neutralization of human adenovirus and human papillomavirus. Our results implicate common core hydrophobic residues as critical for inhibition of these non-enveloped viruses by the two α-defensins, with specificity provided by charged residues unique to each interaction. We also found that the number of α-defensin molecules bound to the virus was a stronger correlate of the anti-viral potency of the α-defensin mutants than their absolute affinity for the viral capsid. Understanding common characteristics of α-defensins important for non-enveloped virus binding will inform rules that govern the function of these abundant and multifaceted peptides in host defense.

Vyšlo v časopise: Delineation of Interfaces on Human Alpha-Defensins Critical for Human Adenovirus and Human Papillomavirus Inhibition. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004360
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004360

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