Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms.

Aprille Seidel, Ying Ye, Lesley R de Armas, Maira Soto, William Yarosh, Renee Andrea Marcsisin-Rogers, Dat Tran, Michael E Selsted, David Camerini

Research output: Contribution to journalArticleResearchpeer-review

50 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1 - 9
Number of pages9
JournalPLoS ONE
Volume5
Issue number3 (Art. No: e9737)
DOIs
Publication statusPublished - 2010
Externally publishedYes

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