2.50
Hdl Handle:
http://hdl.handle.net/10033/579574
Title:
A molecular tweezer antagonizes seminal amyloids and HIV infection.
Authors:
Lump, Edina; Castellano, Laura M; Meier, Christoph; Seeliger, Janine; Erwin, Nelli; Sperlich, Benjamin; Stürzel, Christina M; Usmani, Shariq; Hammond, Rebecca M; von Einem, Jens; Gerold, Gisa; Kreppel, Florian; Bravo-Rodriguez, Kenny; Pietschmann, Thomas; Holmes, Veronica M; Palesch, David; Zirafi, Onofrio; Weissman, Drew; Sowislok, Andrea; Wettig, Burkhard; Heid, Christian; Kirchhoff, Frank; Weil, Tanja; Klärner, Frank-Gerrit; Schrader, Thomas; Bitan, Gal; Sanchez-Garcia, Elsa; Winter, Roland; Shorter, James; Münch, Jan
Abstract:
Semen 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.
Affiliation:
Institute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Citation:
A molecular tweezer antagonizes seminal amyloids and HIV infection. 2015, 4: Elife
Journal:
eLife
Issue Date:
2015
URI:
http://hdl.handle.net/10033/579574
DOI:
10.7554/eLife.05397
PubMed ID:
26284498
Type:
Article
Language:
en
ISSN:
2050-084X
Appears in Collections:
publications of the department experimental Virology([TC]EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorLump, Edinaen
dc.contributor.authorCastellano, Laura Men
dc.contributor.authorMeier, Christophen
dc.contributor.authorSeeliger, Janineen
dc.contributor.authorErwin, Nellien
dc.contributor.authorSperlich, Benjaminen
dc.contributor.authorStürzel, Christina Men
dc.contributor.authorUsmani, Shariqen
dc.contributor.authorHammond, Rebecca Men
dc.contributor.authorvon Einem, Jensen
dc.contributor.authorGerold, Gisaen
dc.contributor.authorKreppel, Florianen
dc.contributor.authorBravo-Rodriguez, Kennyen
dc.contributor.authorPietschmann, Thomasen
dc.contributor.authorHolmes, Veronica Men
dc.contributor.authorPalesch, Daviden
dc.contributor.authorZirafi, Onofrioen
dc.contributor.authorWeissman, Drewen
dc.contributor.authorSowislok, Andreaen
dc.contributor.authorWettig, Burkharden
dc.contributor.authorHeid, Christianen
dc.contributor.authorKirchhoff, Franken
dc.contributor.authorWeil, Tanjaen
dc.contributor.authorKlärner, Frank-Gerriten
dc.contributor.authorSchrader, Thomasen
dc.contributor.authorBitan, Galen
dc.contributor.authorSanchez-Garcia, Elsaen
dc.contributor.authorWinter, Rolanden
dc.contributor.authorShorter, Jamesen
dc.contributor.authorMünch, Janen
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.en
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

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