cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms循环和非循环defensins抑制人类免疫缺陷病毒1型复制通过不同的机制.pdfVIP

Cyclic and Acyclic Defensins Inhibit Human Immunodeficiency Virus Type-1 Replication by Different Mechanisms Aprille Seidel1,2, Ying Ye1,2, Lesley R. de Armas1,2, Maira Soto1,2, William Yarosh1,2, Renee A. Marcsisin1,2, 2,3¤a 2,3¤a 1,2 ¤b Dat Tran , Michael E. Selsted , David Camerini * 1 Department of Molecular Biology and Biochemistry, School of Biological Sciences and Center for Virus Research, University of California Irvine, Irvine, California, United States of America, 2 Center for Immunology, University of California Irvine, Irvine, California, United States of America, 3 Department of Pathology and Laboratory Medicine, School of Medicine, University of California Irvine, Irvine, California, United States of America Abstract Defensins are antimicrobial peptides expressed by plants and animals. In mammals there are three subfamilies of defensins, distinguished by structural features: a, b and h. Alpha and b-defensins are linear peptides with broad anti-microbial activity that are expressed by many mammals including humans. In contrast, h-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 (a), HBD-2 (b) and RTD-1 (h). 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