Journal
JOURNAL OF VIROLOGY
Volume 84, Issue 8, Pages 4041-4049Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.02471-09
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Funding
- NIH [HL054352, EY11431]
- Immunology and Microbial Sciences Summer Program at TSRI
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Human alpha-defensins are evolutionarily conserved effectors of the innate immune response with broadly acting antibacterial activity. Their role in antiviral immunity is less well understood. We previously showed that these antimicrobial peptides are potent inhibitors of human adenovirus infection. Based on biochemical studies and indirect evidence from confocal microscopy, we proposed that defensins bind to and stabilize the virus capsid and neutralize infection by preventing the release of the endosomalytic protein VI. To determine whether defensin action also restricts exposure of the viral genome, we developed a system to evaluate adenovirus uncoating during cell entry by monitoring the exposure of BrdU-labeled viral genomes. This assay allowed us to determine the kinetics of uncoating of virus particles in single cells. Using this assay, we now provide direct evidence that human alpha-defensins block adenovirus infection by preventing uncoating during cell entry.
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