Single-Chain Soluble BG505.SOSIP gp140 Trimers as Structural and Antigenic Mimics of Mature Closed HIV-1 Env

Journal of Virology
Ivelin S GeorgievPeter D Kwong

Abstract

Similar to other type I fusion machines, the HIV-1 envelope glycoprotein (Env) requires proteolytic activation; specifically, cleavage of a gp160 precursor into gp120 and gp41 subunits creates an N-terminal gp41 fusion peptide and permits folding from an immature uncleaved state to a mature closed state. While the atomic-level consequences of cleavage for HIV-1 Env are still being determined, the uncleaved state is antigenically distinct from the mature closed state, and cleavage has been reported to be essential for mimicry of the mature viral spike by soluble versions of Env. Here we report the redesign of a current state-of-the-art soluble Env mimic, BG505.SOSIP, to make it cleavage independent. Specifically, we replaced the furin cleavage site between gp120 and gp41 with Gly-Ser linkers of various lengths. The resultant linked gp120-gp41 constructs, termed single-chain gp140 (sc-gp140), exhibited different levels of structural and antigenic mimicry of the parent cleaved BG505.SOSIP. When constructs were subjected to negative selection to remove subspecies recognized by poorly neutralizing antibodies, trimers of high antigenic mimicry of BG505.SOSIP could be obtained; negative-stain electron microscopy indicated these to res...Continue Reading

References

Aug 1, 1991·The Journal of Experimental Medicine·Q J Sattentau, J P Moore
Jan 1, 1993·Cell Biophysics·J S HustonH Oppermann
Aug 31, 2000·Annual Review of Biochemistry·J J Skehel, D C Wiley
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Zhexin XiangBarry Honig
Apr 3, 2003·Nature Reviews. Molecular Cell Biology·Peter M Colman, Michael C Lawrence
May 22, 2004·BioTechniques·Gabriele KüttnerWolfgang Höhne
Sep 27, 2005·Journal of Structural Biology·David N Mastronarde
Mar 23, 2006·Annual Review of Immunology·Ralph Pantophlet, Dennis R Burton
Jul 25, 2006·Journal of Structural Biology·Guang TangSteven J Ludtke
May 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Donald N ForthalTran Phan
Oct 15, 2009·Annual Review of Medicine·James A Hoxie
Apr 1, 2011·The Journal of Infectious Diseases·Paul SpearmanUNKNOWN HIV Vaccine Trials Network of NIAID
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Audray HarrisSriram Subramaniam
Aug 19, 2011·Nature·Laura M WalkerPascal Poignard
Oct 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Brian MoldtDennis R Burton
Oct 30, 2012·Nature·Florian KleinMichel C Nussenzweig
Jun 19, 2013·Immunological Reviews·Kathryn E Stephenson, Dan H Barouch
Aug 24, 2013·Nature Reviews. Immunology·Peter D KwongGary J Nabel
Sep 14, 2013·Science·Florian KleinMichel C Nussenzweig
Oct 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rajesh P RingeJohn P Moore

❮ Previous
Next ❯

Citations

Feb 13, 2016·Trends in Immunology·Steven W de TaeyeRogier W Sanders
Dec 15, 2015·Expert Review of Vaccines·Kwinten Sliepen, Rogier W Sanders
Jun 9, 2015·Cell Reports·Laura K PritchardMax Crispin
Jun 9, 2016·Current Opinion in Immunology·Kathryn E StephensonDan H Barouch
Aug 2, 2016·Nature Structural & Molecular Biology·M Gordon JoycePeter D Kwong
Jan 18, 2017·Expert Opinion on Biological Therapy·Kristen W Cohen, Nicole Frahm
Jan 31, 2017·Immunological Reviews·Gunilla B Karlsson HedestamRichard T Wyatt
Jan 31, 2017·Immunological Reviews·Rogier W Sanders, John P Moore
Jan 31, 2017·Immunological Reviews·Andrew B Ward, Ian A Wilson
Mar 14, 2017·PloS One·Colleen R CourtneyRalf Dürr
Dec 13, 2017·Frontiers in Immunology·Martina SoldemoGunilla B Karlsson Hedestam
Apr 6, 2018·Journal of Virology·Luis R Castillo-MenendezJoseph Sodroski
Jun 12, 2018·Plant Biotechnology Journal·Emmanuel MargolinAnn E Meyers
Jun 29, 2016·Nature Communications·Linling HeJiang Zhu
May 22, 2019·Journal of the American Society for Mass Spectrometry·Vera B IvlevaQ Paula Lei
Nov 27, 2018·Science Advances·Linling HeJiang Zhu
Sep 14, 2018·Retrovirology·Alba Torrents de la Peña, Rogier W Sanders
Oct 13, 2017·NPJ Vaccines·Baoshan ZhangPeter D Kwong
Aug 26, 2016·Current Opinion in HIV and AIDS·Penny L Moore, Carolyn Williamson
Sep 21, 2017·Frontiers in Immunology·Martina Soldemo, Gunilla B Karlsson Hedestam
May 30, 2019·Frontiers in Immunology·Michael TuenRalf Duerr
Dec 4, 2019·Expert Review of Vaccines·Iván Del Moral-Sánchez, Kwinten Sliepen
Nov 19, 2019·Frontiers in Plant Science·Emmanuel MargolinEdward P Rybicki
Dec 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kyung Soo ParkJames J Moon

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.