Mechanism of adenovirus neutralization by Human alpha-defensins.
Defensins are naturally occurring antimicrobial peptides that disrupt bacterial membranes and prevent bacterial invasion of the host. Emerging studies indicate that certain defensins also block virus infection; however, the mechanism(s) involved are poorly understood. We demonstrate that human alpha-defensins inhibit adenovirus infection at low micromolar concentrations, and this requires direct association of the defensin with the virus. Moreover, defensins inhibit virus disassembly at the vertex region, thereby restricting the release of an internal capsid protein, pVI, which is required for endosomal membrane penetration during cell entry. As a consequence, defensins hamper the release of adenovirus particles from endocytic vesicles, resulting in virion accumulation in early endosomes and lysosomes. Thus, defensins possess remarkably distinct modes of activity against bacteria and viruses, and their function may provide insights for the development of new antiviral strategies.
Smith
Jason G
JG
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nemerow
Glen R
GR
D000256:Adenoviridae / Q000145:classification / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity*; D000890:Anti-Infective Agents / Q000378:metabolism / Q000494:pharmacology; D002213:Capsid / Q000378:metabolism; D002460:Cell Line; D011992:Endosomes / Q000821:virology; D006801:Humans; D012703:Serotyping; D014771:Virion / Q000187:drug effects / Q000378:metabolism; D019065:Virus Assembly; D014779:Virus Replication; D023084:alpha-Defensins / Q000378:metabolism / Q000494:pharmacology*; D023083:beta-Defensins / Q000378:metabolism / Q000494:pharmacology
D000890:Anti-Infective Agents; C500225:DEFA5 protein, human; C106641:DEFB4A protein, human; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1