title: A systematic study of the N-glycosylation sites of HIV-1 envelope protein on infectivity and antibody-mediated neutralization.
abstract: BACKGROUND
  Glycans on the human immunodeficiency virus (HIV) envelope glycoprotein (Env) play an important role in viral infection and evasion of neutralization by antibodies. In this study, all 25 potential N-linked glycosylation sites (PNGS) on the HIV-1 CRF07_BC Env, FE, were mutated individually to study the effect of their removal on viral infectivity, virion production, and antibody-mediated neutralization.
  
  
  RESULTS
  Removal of specific N-glycosylation sites has a significant effect on viral infectivity and antibody-mediated neutralization phenotype. Six of these glycosylation mutants located on the V1/V2 and C1/C2 domains lost infectivity. PNGS mutations located on V4/C4/V5 (except N392 on V4), were shown to increase viral infectivity. Furthermore, FE is much more dependent on specific glycans than clade B Env YU-2. On neutralization effect, PNGS mutations at N197 (C2), N301 (V3), N442 (C4) and N625 (gp41) rendered the virus more susceptible to neutralization by the monoclonal antibodies (MAbs) that recognize the CD4 binding site or gp41. Generally, mutations on V4/V5 loops, C2/C3/C4 regions and gp41 reduced the neutralization sensitivity to PG16. However, mutation of N289 (C2) made the virus more sensitive to both PG9 and PG16. Furthermore, we showed that mutations at N142 (V1), N355 (C3) and N463 (V5) conferred resistance to neutralization by anti-gp41 MAbs. We used the available structural information of HIV Env and homology modeling to provide a structural basis for the observed biological effects of these mutations.
  
  
  CONCLUSIONS
  This report provides the first systematic experimental account of the biological role of the entire PNGS on an HIV-1 Env, which should provide valuable insights for understanding the function of Env in HIV infection cycle and for developing future anti-HIV strategies.
authors: Department of Cell Biology, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Beijing 100050, P.R. China.
authors: Wenbo
authors: W
authors: Wang
authors: Jianhui
authors: J
authors: Nie
authors: Courtney
authors: C
authors: Prochnow
authors: Carolyn
authors: C
authors: Truong
authors: Zheng
authors: Z
authors: Jia
authors: Suting
authors: S
authors: Wang
authors: Xiaojiang S
authors: XS
authors: Chen
authors: Youchun
authors: Y
authors: Wang
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D006031:Glycosylation; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D009500:Neutralization Tests; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus
references: Nat Immunol. 2004 Mar;5(3):233-6
references: 14985706
references: J Virol. 2008 Jan;82(2):638-51
references: 17959660
references: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11440-5
references: 21709254
references: PLoS Pathog. 2010 May 06;6(5):e1000880
references: 20463810
references: Science. 2011 Nov 25;334(6059):1097-103
references: 21998254
references: Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1166-71
references: 20080564
references: Science. 2009 Oct 9;326(5950):285-9
references: 19729618
references: Nature. 2011 Nov 23;480(7377):336-43
references: 22113616
references: Virology. 2012 Feb 5;423(1):97-106
references: 22192629
references: AIDS Res Hum Retroviruses. 2005 Feb;21(2):171-89
references: 15725757
references: J Acquir Immune Defic Syndr. 2010 Apr 1;53(4):440-50
references: 20090544
references: Virus Res. 2001 Nov 5;79(1-2):91-101
references: 11551649
references: J Virol. 1993 Nov;67(11):6642-7
references: 7692082
references: J Biol Chem. 1990 Jun 25;265(18):10373-82
references: 2355006
references: J Virol. 1992 Sep;66(9):5516-24
references: 1501286
references: J Biol Chem. 2008 Nov 21;283(47):32644-9
references: 18815131
references: J Acquir Immune Defic Syndr. 2008 Apr 15;47(5):535-43
references: 18209676
references: J Virol. 1991 Apr;65(4):2119-23
references: 2002555
references: J Virol. 2003 Jan;77(1):642-58
references: 12477867
references: Biochemistry. 2008 Jul 29;47(30):7788-95
references: 18597484
references: Virology. 2003 Aug 15;313(1):117-25
references: 12951026
references: Science. 2011 Sep 16;333(6049):1593-602
references: 21835983
references: J Virol. 2001 Nov;75(22):10892-905
references: 11602729
references: Science. 1998 Jun 19;280(5371):1884-8
references: 9632381
references: PLoS Pathog. 2010 Dec 23;6(12):e1001249
references: 21203482
references: J Virol. 2002 Jul;76(14):7293-305
references: 12072528
references: Biol Chem. 2012 Aug;393(8):719-30
references: 22944675
references: J Virol. 2004 Dec;78(23):13232-52
references: 15542675
references: J Virol. 2002 Jul;76(14):7306-21
references: 12072529
references: Nature. 1998 Jun 18;393(6686):648-59
references: 9641677
references: Nature. 2007 Feb 15;445(7129):732-7
references: 17301785
references: J Virol. 2003 Jan;77(1):560-70
references: 12477860
references: J Biol Chem. 2011 Dec 16;286(50):42900-10
references: 22006924
references: Nature. 2008 Sep 4;455(7209):109-13
references: 18668044
references: J Biol Chem. 1995 Oct 13;270(41):23883-6
references: 7592573
references: Virus Res. 2011 Jan;155(1):137-46
references: 20875470
references: J Proteome Res. 2009 Sep;8(9):4231-42
references: 19610667
references: Nature. 1997 May 22;387(6631):426-30
references: 9163431
references: J Virol. 2012 Feb;86(4):2153-64
references: 22156525
references: Adv Virus Res. 2005;64:231-61
references: 16139596
references: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3739-44
references: 18322015
references: J Virol. 1997 Oct;71(10):7478-87
references: 9311827
references: Nature. 2003 Mar 20;422(6929):307-12
references: 12646921
references: PLoS Pathog. 2011 Sep;7(9):e1002200
references: 21909262
references: Science. 2001 Aug 10;293(5532):1155-9
references: 11498595
references: J Exp Med. 2011 Jul 4;208(7):1419-33
references: 21646396
references: Vaccine. 2011 Nov 8;29(48):9064-74
references: 21945958
references: J Virol. 2005 Aug;79(16):10108-25
references: 16051804
references: J Virol. 2008 Jun;82(11):5417-28
references: 18353944
references: Curr Pharm Des. 2010;16(33):3744-53
references: 21128885
references: Science. 2005 Nov 11;310(5750):1025-8
references: 16284180
references: Virology. 2003 Sep 30;314(2):636-49
references: 14554091
references: Annu Rev Biochem. 1972;41:673-702
references: 4563441
references: J Virol. 2001 Apr;75(7):3435-43
references: 11238869
references: J Biol Chem. 2001 Apr 20;276(16):13433-41
references: 11278567
references: Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12303-8
references: 9356444
references: Nature. 2005 Feb 24;433(7028):834-41
references: 15729334
references: J Virol. 1998 May;72(5):4485-91
references: 9557746
references: Science. 2010 Aug 13;329(5993):811-7
references: 20616231
references: Retrovirology. 2011 May 14;8:37
references: 21569545
references: J Virol. 2010 May;84(9):4311-20
references: 20164234