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dc.contributor.authorLump, Edina
dc.contributor.authorCastellano, Laura M
dc.contributor.authorMeier, Christoph
dc.contributor.authorSeeliger, Janine
dc.contributor.authorErwin, Nelli
dc.contributor.authorSperlich, Benjamin
dc.contributor.authorStürzel, Christina M
dc.contributor.authorUsmani, Shariq
dc.contributor.authorHammond, Rebecca M
dc.contributor.authorvon Einem, Jens
dc.contributor.authorGerold, Gisa
dc.contributor.authorKreppel, Florian
dc.contributor.authorBravo-Rodriguez, Kenny
dc.contributor.authorPietschmann, Thomas
dc.contributor.authorHolmes, Veronica M
dc.contributor.authorPalesch, David
dc.contributor.authorZirafi, Onofrio
dc.contributor.authorWeissman, Drew
dc.contributor.authorSowislok, Andrea
dc.contributor.authorWettig, Burkhard
dc.contributor.authorHeid, Christian
dc.contributor.authorKirchhoff, Frank
dc.contributor.authorWeil, Tanja
dc.contributor.authorKlärner, Frank-Gerrit
dc.contributor.authorSchrader, Thomas
dc.contributor.authorBitan, Gal
dc.contributor.authorSanchez-Garcia, Elsa
dc.contributor.authorWinter, Roland
dc.contributor.authorShorter, James
dc.contributor.authorMünch, Jan
dc.date.accessioned2015-10-12T13:38:58Zen
dc.date.available2015-10-12T13:38:58Zen
dc.date.issued2015en
dc.identifier.citationA molecular tweezer antagonizes seminal amyloids and HIV infection. 2015, 4: Elifeen
dc.identifier.issn2050-084Xen
dc.identifier.pmid26284498en
dc.identifier.doi10.7554/eLife.05397en
dc.identifier.urihttp://hdl.handle.net/10033/579574en
dc.description.abstractSemen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.
dc.language.isoenen
dc.titleA molecular tweezer antagonizes seminal amyloids and HIV infection.en
dc.typeArticleen
dc.contributor.departmentInstitute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.en
dc.identifier.journaleLifeen
refterms.dateFOA2018-06-13T16:00:54Z
html.description.abstractSemen is the main vector for HIV transmission and contains amyloid fibrils that enhance viral infection. Available microbicides that target viral components have proven largely ineffective in preventing sexual virus transmission. In this study, we establish that CLR01, a 'molecular tweezer' specific for lysine and arginine residues, inhibits the formation of infectivity-enhancing seminal amyloids and remodels preformed fibrils. Moreover, CLR01 abrogates semen-mediated enhancement of viral infection by preventing the formation of virion-amyloid complexes and by directly disrupting the membrane integrity of HIV and other enveloped viruses. We establish that CLR01 acts by binding to the target lysine and arginine residues rather than by a non-specific, colloidal mechanism. CLR01 counteracts both host factors that may be important for HIV transmission and the pathogen itself. These combined anti-amyloid and antiviral activities make CLR01 a promising topical microbicide for blocking infection by HIV and other sexually transmitted viruses.


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