Mannose-rich glycosylation patterns on HIV-1 subtype C gp120 and sensitivity to the lectins, Griffithsin, Cyanovirin-N and Scytovirin.
Griffithsin (GRFT), Cyanovirin-N (CV-N) and Scytovirin (SVN) are lectins that inhibit HIV-1 infection by binding to multiple mannose-rich glycans on the HIV-1 envelope glycoproteins (Env). Here we show that these lectins neutralize subtype C primary virus isolates in addition to Env-pseudotyped viruses obtained from plasma and cervical vaginal lavages. Among 15 subtype C pseudoviruses, the median IC(50) values were 0.4, 1.8 and 20.1nM for GRFT, CV-N and SVN, respectively, similar to what was found for subtype B and A. Analysis of Env sequences suggested that concomitant lack of glycans at positions 234 and 295 resulted in natural resistance to these compounds, which was confirmed by site-directed mutagenesis. Furthermore, the binding sites for these lectins overlapped that of the 2G12 monoclonal antibody epitope, which is generally absent on subtype C Env. This data support further research on these lectins as potential microbicides in the context of HIV-1 subtype C infection.
Alexandre
Kabamba B
KB
National Institute for Communicable Diseases, Johannesburg, South Africa.
Gray
Elin S
ES
Lambson
Bronwen E
BE
Moore
Penny L
PL
Choge
Isaac A
IA
Mlisana
Koleka
K
Karim
Salim S Abdool
SS
McMahon
James
J
O'Keefe
Barry
B
Chikwamba
Rachel
R
Morris
Lynn
L
D000328:Adult; D020418:Algal Proteins / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D001665:Binding Sites; D002352:Carrier Proteins / Q000494:pharmacology*; D005260:Female; D006031:Glycosylation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D037102:Lectins / Q000494:pharmacology*; D008358:Mannose / Q000378:metabolism*; D008565:Membrane Proteins; D008826:Microbial Sensitivity Tests; D009500:Neutralization Tests; D037121:Plant Lectins; D010949:Plasma / Q000821:virology; D011485:Protein Binding; D014621:Vagina / Q000821:virology; D055815:Young Adult
D020418:Algal Proteins; D000998:Antiviral Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015699:HIV Envelope Protein gp120; D037102:Lectins; D008565:Membrane Proteins; D037121:Plant Lectins; C514793:gp120 protein, Human immunodeficiency virus 1; C474342:scytovirin protein, S varium; C107733:cyanovirin N; D008358:Mannose; C499654:griffithsin protein, Griffithsia
J Virol. 1997 Mar;71(3):2512-7
9032392
Protein Sci. 2007 Dec;16(12):2756-60
17965185
Acta Biochim Pol. 2006;53(4):617-26
17128290
Nat Rev Microbiol. 2003 Oct;1(1):25-34
15040177
J Proteome Res. 2009 Sep;8(9):4231-42
19610667
J Virol. 1999 May;73(5):4360-71
10196334
AIDS Res Hum Retroviruses. 2001 Nov 1;17(16):1527-31
11709097
Protein Expr Purif. 2006 Apr;46(2):233-9
16289703
Science. 2003 Jun 27;300(5628):2065-71
12829775
J Virol. 2006 Dec;80(23):11776-90
16971434
J Virol. 2005 Jun;79(12):7777-84
15919930
Prog Biophys Mol Biol. 2005 Jun;88(2):233-82
15572157
J Virol. 2007 Oct;81(19):10769-76
17634239
Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6099-104
19332801
Lancet. 2007 Mar 3;369(9563):787-797
17336656
AIDS. 2005 May 20;19(8):833-5
15867500
Virology. 2007 Nov 10;368(1):145-54
17658575
J Virol. 2004 Dec;78(23):13232-52
15542675
J Virol. 2002 Jul;76(14):7306-21
12072529
Antimicrob Agents Chemother. 1997 Jul;41(7):1521-30
9210678
J Virol. 2002 Jul;76(14):7293-305
12072528
J Virol. 2006 Sep;80(17):8411-21
16912292
Glycobiology. 2004 Dec;14(12):1229-46
15175256
Int J Biochem Cell Biol. 2008;40(12):2802-14
18598778
Structure. 2006 Jul;14(7):1127-35
16843894
AIDS Res Hum Retroviruses. 2002 May 20;18(8):567-76
12036486
Trends Immunol. 2001 Dec;22(12):643-6
11738974
Nature. 2003 Mar 20;422(6929):307-12
12646921
PLoS One. 2009;4(2):e4505
19229336
J Acquir Immune Defic Syndr. 2005 Dec 15;40(5):512-20
16284525
Biochemistry. 2003 Mar 11;42(9):2578-84
12614152
J Biol Chem. 2005 Mar 11;280(10):9345-53
15613479
J Virol. 2005 Aug;79(16):10108-25
16051804
AIDS Res Hum Retroviruses. 2003 Jul;19(7):535-41
12921090
AIDS Res Hum Retroviruses. 2000 Dec 10;16(18):2019-35
11153085
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12972-7
14557540
J Virol. 2007 Jun;81(12):6187-96
17409164
Mol Pharmacol. 2001 May;59(5):949-54
11306674
Lancet Infect Dis. 2008 Nov;8(11):685-97
18992405
Nat Rev Immunol. 2006 May;6(5):371-82
16639430
N Engl J Med. 2007 May 17;356(20):2073-81
17507706
Lancet Infect Dis. 2005 Nov;5(11):726-31
16253890
Structure. 2002 May;10(5):673-86
12015150
J Virol. 1999 May;73(5):4393-403
10196337
AIDS Res Hum Retroviruses. 2004 Jan;20(1):11-8
15000694
PLoS Med. 2006 Jul;3(7):e255
16834457
AIDS Res Hum Retroviruses. 2006 May;22(5):458-65
16706624
Curr Protoc Immunol. 2005 Jan;Chapter 12:12.11.1-12.11.17
18432938