Reprogramming of red blood cell metabolism in Zika virus-infected donors.
Zika virus
erythrocyte
lipidomics
metabolic reprogramming
metabolomics
viral infection
Journal
Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
24
02
2022
received:
15
01
2022
accepted:
24
02
2022
pubmed:
15
3
2022
medline:
11
5
2022
entrez:
14
3
2022
Statut:
ppublish
Résumé
Diseases caused by arthropod-borne viruses remain a burden to global health; in particular, Zika virus (ZIKV) has been reported in 87 countries and territories. In healthy blood donors, ZIKV RNA can be detected in red blood cells (RBCs) months after infection, clearance of detectable nucleic acid in plasma, and seroconversion. However, little information is available on the impact of ZIKV infection to metabolism. We applied mass spectrometry-based metabolomics and lipidomics approaches to investigate the impact of ZIKV infection on RBCs over the course of infection. ZIKV-infected blood donors (n = 25) were identified through molecular and serologic methods, which included nucleic acid amplification testing and real-time polymerase chain reaction (PCR) for detection of ZIKV RNA and enzyme-linked immunosorbent assay (ELISA) for detection of flavivirus-specific IgM and IgG. In ZIKV RNA-positive donors, we observed lower glucose and lactate levels, and higher levels of ribose phosphate, suggestive of the activation of the pentose phosphate pathway. The top pathways altered in RBCs from ZIKV-IgM-positive donors include amino acid metabolism and biosynthesis, fatty acid metabolism and biosynthesis, linoleic acid and arachidonate metabolism and glutathione metabolism. RBCs from ZIKV-infected donors had increased levels of early glycolytic metabolites, and higher levels of metabolites of the pentose phosphate pathway. Alterations in acyl-carnitine and fatty acid metabolism are consistent with impaired membrane lipid homeostasis in RBCs from ZIKV IgM positive donors. RBC from healthy blood donors who had been infected by ZIKV are characterized by long-lasting metabolic alterations even months after infection has resolved.
Sections du résumé
BACKGROUND
Diseases caused by arthropod-borne viruses remain a burden to global health; in particular, Zika virus (ZIKV) has been reported in 87 countries and territories. In healthy blood donors, ZIKV RNA can be detected in red blood cells (RBCs) months after infection, clearance of detectable nucleic acid in plasma, and seroconversion. However, little information is available on the impact of ZIKV infection to metabolism.
STUDY DESIGN AND METHODS
We applied mass spectrometry-based metabolomics and lipidomics approaches to investigate the impact of ZIKV infection on RBCs over the course of infection. ZIKV-infected blood donors (n = 25) were identified through molecular and serologic methods, which included nucleic acid amplification testing and real-time polymerase chain reaction (PCR) for detection of ZIKV RNA and enzyme-linked immunosorbent assay (ELISA) for detection of flavivirus-specific IgM and IgG.
RESULTS
In ZIKV RNA-positive donors, we observed lower glucose and lactate levels, and higher levels of ribose phosphate, suggestive of the activation of the pentose phosphate pathway. The top pathways altered in RBCs from ZIKV-IgM-positive donors include amino acid metabolism and biosynthesis, fatty acid metabolism and biosynthesis, linoleic acid and arachidonate metabolism and glutathione metabolism. RBCs from ZIKV-infected donors had increased levels of early glycolytic metabolites, and higher levels of metabolites of the pentose phosphate pathway. Alterations in acyl-carnitine and fatty acid metabolism are consistent with impaired membrane lipid homeostasis in RBCs from ZIKV IgM positive donors.
CONCLUSION
RBC from healthy blood donors who had been infected by ZIKV are characterized by long-lasting metabolic alterations even months after infection has resolved.
Identifiants
pubmed: 35285520
doi: 10.1111/trf.16851
pmc: PMC9086146
mid: NIHMS1790268
doi:
Substances chimiques
Antibodies, Viral
0
Fatty Acids
0
Immunoglobulin M
0
RNA, Viral
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1045-1064Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL146442
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201100001I
Pays : United States
Organisme : NIGMS NIH HHS
ID : RM1 GM131968
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL161004
Pays : United States
Organisme : HHS
ID : HHSO100201600010C
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL146442
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL149714
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL148151
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148151
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL150032
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL149714
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21HL150032
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01HL161004
Pays : United States
Organisme : WHI NIH HHS
ID : HHSN268201100001C
Pays : United States
Informations de copyright
© 2022 AABB.
Références
Transfusion. 2021 Jun;61(6):1867-1883
pubmed: 33904180
Blood. 2013 Mar 14;121(11):2099-107
pubmed: 23349388
Transfusion. 2020 Jun;60(6):1212-1226
pubmed: 32339326
Front Immunol. 2019 Jul 11;10:1617
pubmed: 31354746
Free Radic Biol Med. 2016 Jul;96:152-65
pubmed: 27094493
Blood Adv. 2017 Jun 27;1(15):1132-1141
pubmed: 29034365
Anal Chem. 2010 Dec 1;82(23):9818-26
pubmed: 21049934
Trans R Soc Trop Med Hyg. 1952 Sep;46(5):509-20
pubmed: 12995440
Lancet Infect Dis. 2020 Dec;20(12):1446-1456
pubmed: 32673593
Blood. 2018 Jun 7;131(23):2581-2593
pubmed: 29666112
PLoS One. 2021 Nov 12;16(11):e0259267
pubmed: 34767588
Transfusion. 2021 Jan;61(1):108-123
pubmed: 33073382
Blood Transfus. 2019 Jan;17(1):27-52
pubmed: 30653459
J Proteome Res. 2020 Nov 6;19(11):4455-4469
pubmed: 33103907
Blood. 2021 Apr 29;137(17):2285-2298
pubmed: 33657208
Artif Organs. 2018 Feb;42(2):184-192
pubmed: 28877350
PLoS Negl Trop Dis. 2020 Sep 21;14(9):e0008532
pubmed: 32956416
Blood. 2019 Sep 26;134(13):1003-1013
pubmed: 31350268
Eur J Obstet Gynecol Reprod Biol. 2010 Oct;152(2):126-32
pubmed: 20933151
Transfusion. 2017 Feb;57(2):325-336
pubmed: 27813142
Haematologica. 2022 Jan 01;107(1):112-125
pubmed: 33730845
Blood. 2013 Jul 11;122(2):282-92
pubmed: 23692858
Blood. 2016 Sep 22;128(12):e32-42
pubmed: 27405778
Haematologica. 2016 May;101(5):578-86
pubmed: 26921359
Can J Microbiol. 2020 Feb;66(2):87-98
pubmed: 31682478
J Clin Invest. 2020 May 1;130(5):2270-2285
pubmed: 31961822
Front Med (Lausanne). 2017 Oct 17;4:175
pubmed: 29090212
Front Physiol. 2020 Apr 30;11:396
pubmed: 32425810
mSphere. 2018 Mar 28;3(2):
pubmed: 29600283
Emerg Infect Dis. 2019 Dec;25(12):2264-2265
pubmed: 31742511
N Engl J Med. 2016 Apr 21;374(16):1552-63
pubmed: 27028561
J Virol. 1986 Sep;59(3):768-70
pubmed: 3016341
Br J Haematol. 2021 Feb;192(4):e108-e111
pubmed: 33410504
JCI Insight. 2021 Feb 8;6(3):
pubmed: 33351786
Viruses. 2019 Mar 06;11(3):
pubmed: 30845653
J Immunol. 2018 Sep 1;201(5):1343-1351
pubmed: 30127064
Acta Neuropathol Commun. 2017 Jun 23;5(1):50
pubmed: 28645311
Transfusion. 2021 May;61(5):1586-1599
pubmed: 33830505
J Infect Dis. 2017 Dec 16;216(suppl_10):S935-S944
pubmed: 29267925
BMC Infect Dis. 2019 Nov 21;19(1):986
pubmed: 31752731
Elife. 2021 Mar 16;10:
pubmed: 33724185
Haematologica. 2022 Jan 01;107(1):298-302
pubmed: 34498445
Kidney Int. 2021 Dec;100(6):1227-1239
pubmed: 34537228
J Virol. 2020 Oct 14;94(21):
pubmed: 32847848
Transfusion. 2019 Aug;59(8):2537-2543
pubmed: 31074905
PLoS Negl Trop Dis. 2020 Aug 3;14(8):e0008424
pubmed: 32745093
Lancet. 2017 Nov 4;390(10107):2099-2109
pubmed: 28647173
Virulence. 2012 Jul 1;3(4):351-67
pubmed: 22722247
J Am Chem Soc. 2011 Oct 12;133(40):16251-7
pubmed: 21892828
Antiviral Res. 2016 Jun;130:69-80
pubmed: 26996139
Cell Metab. 2022 Feb 1;34(2):299-316.e6
pubmed: 35108516
Sci Rep. 2016 Oct 19;6:35296
pubmed: 27759009
JCI Insight. 2020 Jul 23;5(14):
pubmed: 32559180
Transfusion. 2020 Jun;60(6):1197-1211
pubmed: 32394461
Blood Adv. 2019 Aug 13;3(15):2272-2285
pubmed: 31350307
Stem Cell Rev Rep. 2022 Jun;18(5):1809-1821
pubmed: 35181867
Front Immunol. 2020 Aug 27;11:1964
pubmed: 32983129
Sci Rep. 2017 Apr 07;7:46249
pubmed: 28387366
Science. 2016 Apr 22;352(6284):467-70
pubmed: 27033547
J Infect Dis. 2010 Aug 15;202(4):624-32
pubmed: 20617898
Front Physiol. 2019 Aug 14;10:923
pubmed: 31474870
Blood. 2008 Jan 15;111(2):905-14
pubmed: 17911385
Nat Commun. 2019 Oct 18;10(1):4766
pubmed: 31628327
Nat Microbiol. 2020 Jun;5(6):796-812
pubmed: 32367055
Clin Infect Dis. 2007 Jul 15;45(2):181-6
pubmed: 17578776
JCI Insight. 2021 Jul 22;6(14):
pubmed: 34138756
Haematologica. 2021 May 01;106(5):1290-1302
pubmed: 32241843
J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jan 15;1009-1010:44-54
pubmed: 26708624
Nucleic Acids Res. 2018 Jul 2;46(W1):W486-W494
pubmed: 29762782
Transfusion. 2018 Jan;58(1):34-40
pubmed: 29063631
Free Radic Biol Med. 2014 Nov;76:107-13
pubmed: 25108189
Blood Transfus. 2020 Mar;18(2):130-142
pubmed: 32203008
Transfusion. 2015 Jun;55(6):1178-85
pubmed: 25644965
Int J Mol Sci. 2021 Jan 18;22(2):
pubmed: 33477427
Mol Nutr Food Res. 2005 Nov;49(11):1063-71
pubmed: 16270279
Transfusion. 2021 Feb;61(2):435-448
pubmed: 33146433
Methods Mol Biol. 2019;1978:121-135
pubmed: 31119660
Clin Microbiol Infect. 2017 May;23(5):296-305
pubmed: 28062314
Virus Res. 2020 Sep;286:198084
pubmed: 32622852
Cell Rep. 2017 Jan 10;18(2):324-333
pubmed: 28076778
Methods Mol Biol. 2019;1978:13-26
pubmed: 31119654
Cells. 2021 Sep 02;10(9):
pubmed: 34571942
Sci Rep. 2019 May 28;9(1):7930
pubmed: 31138879
Front Physiol. 2014 Jan 30;5:9
pubmed: 24523696
Biomed Res Int. 2016;2016:3429604
pubmed: 27872848
Front Microbiol. 2019 Jul 04;10:1465
pubmed: 31333605
Biochim Biophys Acta. 2007 Dec;1768(12):3235-59
pubmed: 17945183
Transfusion. 2020 Jun;60(6):1160-1174
pubmed: 32385854
Curr Protoc Bioinformatics. 2019 Mar;65(1):e69
pubmed: 30556956
Transfusion. 2020 Apr;60(4):786-798
pubmed: 32104927
Nature. 2022 Mar;603(7899):145-151
pubmed: 35045565
Transfusion. 2020 Jun;60(6):1183-1196
pubmed: 32385922
N Engl J Med. 2018 May 10;378(19):1778-1788
pubmed: 29742375
Sci Rep. 2016 Aug 26;6:32188
pubmed: 27561337
PLoS Negl Trop Dis. 2016 Apr 07;10(4):e0004607
pubmed: 27055163
Cell Rep Med. 2020 May 19;1(2):100019
pubmed: 32501455
J Microbiol. 2017 Mar;55(3):204-219
pubmed: 28243937
PLoS One. 2019 Mar 20;14(3):e0214016
pubmed: 30893357
Haematologica. 2018 Feb;103(2):361-372
pubmed: 29079593
PLoS Pathog. 2020 Dec 14;16(12):e1009019
pubmed: 33315931
Front Microbiol. 2017 Oct 10;8:1954
pubmed: 29067015
Trans R Soc Trop Med Hyg. 1952 Sep;46(5):521-34
pubmed: 12995441
Br J Haematol. 2018 Jan;180(1):110-117
pubmed: 29143311
Sci Rep. 2016 Jul 20;6:29637
pubmed: 27436223
J Neurosci. 2017 Feb 22;37(8):2161-2175
pubmed: 28123079