Evolution toward beta common chain receptor usage links the matrix proteins of HIV-1 and its ancestors to human erythropoietin.
HIV-1 and HIV-2 ancestors
HIV-1 evolutionary trajectory
HIV-1 matrix protein p17
common beta chain receptor
human erythropoietin
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
12 01 2021
12 01 2021
Historique:
entrez:
29
12
2020
pubmed:
30
12
2020
medline:
19
5
2021
Statut:
ppublish
Résumé
The HIV-1 matrix protein p17 (p17) is a pleiotropic molecule impacting on different cell types. Its interaction with many cellular proteins underlines the importance of the viral protein as a major determinant of human specific adaptation. We previously showed the proangiogenic capability of p17. Here, by integrating functional analysis and receptor binding, we identify a functional epitope that displays molecular mimicry with human erythropoietin (EPO) and promotes angiogenesis through common beta chain receptor (βCR) activation. The functional EPO-like epitope was found to be present in the matrix protein of HIV-1 ancestors SIV originated in chimpanzees (SIVcpz) and gorillas (SIVgor) but not in that of HIV-2 and its ancestor SIVsmm from sooty mangabeys. According to biological data, evolution of the EPO-like epitope showed a clear differentiation between HIV-1/SIVcpz-gor and HIV-2/SIVsmm branches, thus highlighting this epitope on p17 as a divergent signature discriminating HIV-1 and HIV-2 ancestors. P17 is known to enhance HIV-1 replication. Similarly to other βCR ligands, p17 is capable of attracting and activating HIV-1 target cells and promoting a proinflammatory microenvironment. Thus, it is tempting to speculate that acquisition of an epitope on the matrix proteins of HIV-1 ancestors capable of triggering βCR may have represented a critical step to enhance viral aggressiveness and early human-to-human SIVcpz/gor dissemination. The hypothesis that the p17/βCR interaction and βCR abnormal stimulation may also play a role in sustaining chronic activation and inflammation, thus marking the difference between HIV-1 and HIV-2 in term of pathogenicity, needs further investigation.
Identifiants
pubmed: 33372148
pii: 2021366118
doi: 10.1073/pnas.2021366118
pmc: PMC7812818
pii:
doi:
Substances chimiques
EPO protein, human
0
Epitopes
0
HIV Antigens
0
gag Gene Products, Human Immunodeficiency Virus
0
p17 protein, Human Immunodeficiency Virus Type 1
0
Erythropoietin
11096-26-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Competing interest statement: F.C. and A.C. are listed as inventors in a patent application related to this study.
Références
Sci Rep. 2016 Dec 01;6:38027
pubmed: 27905556
J Thromb Haemost. 2012 Sep;10(9):1914-28
pubmed: 22738133
J Virol. 2014 May;88(10):5706-17
pubmed: 24623414
Br J Haematol. 2003 Jan;120(2):337-43
pubmed: 12542496
Cell Host Microbe. 2019 Jan 9;25(1):27-38
pubmed: 30629915
Cell Microbiol. 2008 Mar;10(3):655-66
pubmed: 18042260
J Clin Invest. 2012 May;122(5):1644-52
pubmed: 22505456
Cell Signal. 1998 Oct;10(9):619-28
pubmed: 9794243
J Infect Dis. 2011 Sep 15;204(6):902-11
pubmed: 21849287
Sci Rep. 2017 Sep 4;7(1):10313
pubmed: 28871125
J Biol Chem. 2013 Jan 11;288(2):1150-61
pubmed: 23166320
J Mol Biol. 2000 Jun 2;299(2):359-68
pubmed: 10860744
Mol Syst Biol. 2011 Oct 11;7:539
pubmed: 21988835
Nature. 2011 Dec 21;481(7381):365-70
pubmed: 22190034
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14807-12
pubmed: 16199516
Lab Invest. 2019 Feb;99(2):180-190
pubmed: 30390010
Biochim Biophys Acta Gen Subj. 2019 Jan;1863(1):13-24
pubmed: 30248376
Bioinformatics. 2014 May 1;30(9):1312-3
pubmed: 24451623
J Virol. 2001 Jan;75(2):857-66
pubmed: 11134299
Mol Biol Evol. 1988 Nov;5(6):729-31
pubmed: 3221794
Blood. 1999 Apr 15;93(8):2627-36
pubmed: 10194442
HIV Med. 2016 Feb;17(2):89-105
pubmed: 26452565
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3867-72
pubmed: 18310327
J Virol. 2017 Jul 27;91(16):
pubmed: 28592537
Mol Biol Evol. 1987 Jul;4(4):406-25
pubmed: 3447015
Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14907-12
pubmed: 15456912
Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14580-5
pubmed: 22904195
New Microbiol. 2006 Jan;29(1):1-10
pubmed: 16608119
Blood. 2012 Mar 8;119(10):2274-83
pubmed: 22262769
Cell Host Microbe. 2009 Nov 19;6(5):409-21
pubmed: 19917496
Blood. 2016 Mar 17;127(11):1403-9
pubmed: 26773045
Mucosal Immunol. 2018 Jan;11(1):236-248
pubmed: 28513595
Mol Biol Evol. 2007 Aug;24(8):1853-60
pubmed: 17545188
Cancer Gene Ther. 2020 Oct 22;:
pubmed: 33093643
Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841
pubmed: 22229120
J Virol. 2011 Mar;85(5):2429-38
pubmed: 21159859
Cold Spring Harb Perspect Biol. 2018 Jun 1;10(6):
pubmed: 28716883
J Virol. 2019 May 1;93(10):
pubmed: 30814287
Arterioscler Thromb Vasc Biol. 2014 Apr;34(4):846-56
pubmed: 24482377
J Virol. 2009 Nov;83(21):11318-29
pubmed: 19692478
Curr Opin Pharmacol. 2013 Jun;13(3):351-61
pubmed: 23643194
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9972-7
pubmed: 12105273
AIDS. 2008 Feb 19;22(4):457-68
pubmed: 18301058
J Virol. 2004 Mar;78(5):2319-26
pubmed: 14963128
AIDS. 2009 Mar 13;23(5):549-54
pubmed: 19262354
Am J Physiol. 1998 Sep;275(3):C623-33
pubmed: 9730944
Proc Natl Acad Sci U S A. 1989 Aug;86(15):5781-5
pubmed: 2788277
Syst Biol. 2010 May;59(3):307-21
pubmed: 20525638
J Virol. 1994 Aug;68(8):5311-20
pubmed: 8035531