Theta-defensins prevent HIV-1 Env-mediated fusion by binding gp41 and blocking 6-helix bundle formation

The Journal of Biological Chemistry
Stephen A GalloRobert Blumenthal

Abstract

Retrocyclin-1, a -defensin, protects target cells from human immunodeficiency virus, type 1 (HIV-1) by preventing viral entry. To delineate its mechanism, we conducted fusion assays between susceptible target cells and effector cells that expressed HIV-1 Env. Retrocyclin-1 (4 microm) completely blocked fusion mediated by HIV-1 Envs that used CXCR4 or CCR5 but had little effect on cell fusion mediated by HIV-2 and simian immunodeficiency virus Envs. Retrocyclin-1 inhibited HIV-1 Env-mediated fusion without impairing the lateral mobility of CD4, and it inhibited the fusion of CD4-deficient cells with cells bearing CD4-independent HIV-1 Env. Thus, it could act without cross-linking membrane proteins or inhibiting gp120-CD4 interactions. Retrocyclin-1 acted late in the HIV-1 Env fusion cascade but prior to 6-helix bundle formation. Surface plasmon resonance experiments revealed that retrocyclin bound the ectodomain of gp41 with high affinity in a glycan-independent manner and that it bound selectively to the gp41 C-terminal heptad repeat. Native-PAGE, enzyme-linked immunosorbent assay, and CD spectroscopic analyses all revealed that retrocyclin-1 prevented 6-helix bundle formation. This mode of action, although novel for an innate ...Continue Reading

References

Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·C WildT Matthews
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·C T WildT J Matthews
Nov 1, 1993·AIDS Research and Human Retroviruses·C WildT Matthews
Sep 9, 1993·Nature·S JiangA R Neurath
May 22, 1997·Nature·W WeissenhornD C Wiley
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·K TanM Lu
Apr 18, 1998·Nature Structural Biology·R A FurutaC D Weiss
Aug 26, 1998·The EMBO Journal·M CaffreyG M Clore
Dec 23, 1998·Proceedings of the National Academy of Sciences of the United States of America·D C ChanP S Kim
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·T L HoffmanR W Doms
Jun 8, 1999·Annual Review of Immunology·E A BergerJ M Farber
Mar 7, 2001·Science·M J RootP S Kim
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·D M Eckert, P S Kim
Feb 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Alexander M ColeRobert I Lehrer
Feb 23, 2002·The Journal of Biological Chemistry·Carole A BewleyG Marius Clore
Mar 13, 2003·Molecular Biology of the Cell·Ruben M MarkosyanGrigory B Melikyan
Apr 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei WangRobert I Lehrer
Jul 23, 2003·Biochimica Et Biophysica Acta·Stephen A GalloRobert Blumenthal
Oct 31, 2003·AIDS Research and Human Retroviruses·Carsten MünkAlexander M Cole
Mar 17, 2004·Peptides·Tung X NguyenRobert I Lehrer
Jun 4, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·S M OwenR B Lal
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei WangRobert I Lehrer
Sep 17, 2004·Nature Reviews. Microbiology·Robert I Lehrer
Dec 14, 2004·AIDS Research and Human Retroviruses·Sherry M OwenRobert I Lehrer
Sep 13, 2005·Nature Immunology·Eugenia LeikinaLeonid V Chernomordik
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amy L ColeAlexander M Cole

❮ Previous
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Citations

Jan 12, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Mohamed Zaiou
May 8, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Emily Gwyer FindlayDonald J Davidson
May 22, 2009·Journal of the American Chemical Society·Felix Freire, Samuel H Gellman
Apr 2, 2011·The Journal of Organic Chemistry·Pin-Nan Cheng, James S Nowick
Nov 23, 2007·Natural Product Reports·Dwight D BakerVineet Rajgarhia
Feb 14, 2012·Molecular BioSystems·Andrew GouldJulio A Camarero
Jul 31, 2009·The Journal of Biological Chemistry·Gang WeiWuyuan Lu
Jun 27, 2012·The Journal of Biological Chemistry·Lusine H DemirkhanyanGregory B Melikyan
Sep 11, 2008·The Journal of Biological Chemistry·Aisling S DuganWalter J Atwood
Jun 16, 2012·The Journal of Biological Chemistry·Robert I LehrerMichael E Selsted
May 18, 2007·AIDS Research and Human Retroviruses·Qiuwei WangShen Pang
Nov 30, 2006·Current Opinion in Hematology·Robert I Lehrer
Feb 16, 2011·Antimicrobial Agents and Chemotherapy·A B SassiL C Rohan
Oct 15, 2008·Infection and Immunity·Deborah E DietrichKim A Brogden
Jan 24, 2013·Investigative Ophthalmology & Visual Science·Gilbert G JoseCurtis R Brandt
Apr 21, 2009·Proteome Science·Geert ZegelsXaveer W M Van Ostade
Jul 27, 2007·Retrovirology·Juan Lama, Vicente Planelles
Oct 27, 2007·Retrovirology·Chris Baldwin, Ben Berkhout
Oct 13, 2010·Retrovirology·Persephone BorrowUNKNOWN EUROPRISE Working Group
May 1, 2009·PLoS Biology·Nitya VenkataramanAlexander M Cole
Dec 22, 2009·Future Microbiology·Karl G KohlgrafKim A Brogden
Feb 23, 2013·The Journal of Biological Chemistry·Anne C ConibearDavid J Craik
May 10, 2011·Cellular and Molecular Life Sciences : CMLS·W Todd PenberthyAlexander M Cole
Apr 4, 2012·Expert Opinion on Drug Discovery·David J CraikMasa Cemazar
Aug 27, 2015·Reviews in Medical Virology·Miral FumakiaEmmanuel A Ho
Apr 5, 2016·Proceedings of the National Academy of Sciences of the United States of America·Matthew BrookMohini Gray
Feb 12, 2015·The Biochemical Journal·Elena KudryashovaDmitri S Kudryashov
May 7, 2016·International Journal of Molecular Sciences·Shuai WangShiyan Qiao
Jan 15, 2008·Cell Host & Microbe·Jason G Smith, Glen R Nemerow
May 19, 2017·FEMS Microbiology Reviews·María Eugenia Pachón-IbáñezJavier Sánchez-Céspedes
Jul 21, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Annarita FalangaOlga Scudiero

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