Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms.
AuthorSeidel, A; Ye, Y; de Armas, LR; Soto, M; Yarosh, W; Marcsisin, RA; Tran, D; Selsted, ME; Camerini, D
Source TitlePLoS One
PublisherPublic Library of Science (PLoS)
University of Melbourne Author/sMARCSISIN, RENEE
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsSeidel, A., Ye, Y., de Armas, L. R., Soto, M., Yarosh, W., Marcsisin, R. A., Tran, D., Selsted, M. E. & Camerini, D. (2010). Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms.. PLoS One, 5 (3), pp.e9737-. https://doi.org/10.1371/journal.pone.0009737.
Access StatusOpen Access
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840026
Defensins are antimicrobial peptides expressed by plants and animals. In mammals there are three subfamilies of defensins, distinguished by structural features: alpha, beta and theta. Alpha and beta-defensins are linear peptides with broad anti-microbial activity that are expressed by many mammals including humans. In contrast, theta-defensins are cyclic anti-microbial peptides made by several non-human primates but not humans. All three defensin types have anti-HIV-1 activity, but their mechanisms of action differ. We studied the anti-HIV-1 activity of one defensin from each group, HNP-1 (alpha), HBD-2 (beta) and RTD-1 (theta). We examined how each defensin affected HIV-1 infection and demonstrated that the cyclic defensin RTD-1 inhibited HIV-1 entry, while acyclic HNP-1 and HBD-2 inhibited HIV-1 replication even when added 12 hours post-infection and blocked viral replication after HIV-1 cDNA formation. We further found that all three defensins downmodulated CXCR4. Moreover, RTD-1 inactivated X4 HIV-1, while HNP-1 and HBD-2 inactivated both X4 and R5 HIV-1. The data presented here show that acyclic and cyclic defensins block HIV-1 replication by shared and diverse mechanisms. Moreover, we found that HNP-1 and RTD-1 directly inhibited firefly luciferase enzymatic activity, which may affect the interpretation of previously published data.
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