Zika virus persistence in the male macaque reproductive tract.
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
15
03
2022
accepted:
07
06
2022
revised:
20
07
2022
pubmed:
6
7
2022
medline:
23
7
2022
entrez:
5
7
2022
Statut:
epublish
Résumé
Zika virus (ZIKV) is unique among mosquito-borne flaviviruses in that it is also vertically and sexually transmitted by humans. The male reproductive tract is thought to be a ZIKV reservoir; however, the reported magnitude and duration of viral persistence in male genital tissues vary widely in humans and non-human primate models. ZIKV tissue and cellular tropism and potential effects on male fertility also remain unclear. The objective of this study was to resolve these questions by analyzing archived genital tissues from 51 ZIKV-inoculated male macaques and correlating data on plasma viral kinetics, tissue tropism, and ZIKV-induced pathological changes in the reproductive tract. We hypothesized that ZIKV would persist in the male macaque genital tract for longer than there was detectable viremia, where it would localize to germ and epithelial cells and associate with lesions. We detected ZIKV RNA and infectious virus in testis, epididymis, seminal vesicle, and prostate gland. In contrast to prepubertal males, sexually mature macaques were significantly more likely to harbor persistent ZIKV RNA or infectious virus somewhere in the genital tract, with detection as late as 60 days post-inoculation. ZIKV RNA localized primarily to testicular stem cells/sperm precursors and epithelial cells, including Sertoli cells, epididymal duct epithelium, and glandular epithelia of the seminal vesicle and prostate gland. ZIKV infection was associated with microscopic evidence of inflammation in the epididymis and prostate gland of sexually mature males, pathologies that were absent in uninfected controls, which could have significant effects on male fertility. The findings from this study increase our understanding of persistent ZIKV infection which can inform risk of sexual transmission during assisted reproductive therapies as well as potential impacts on male fertility.
Identifiants
pubmed: 35788751
doi: 10.1371/journal.pntd.0010566
pii: PNTD-D-22-00338
pmc: PMC9299295
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0010566Subventions
Organisme : NIH HHS
ID : P51 OD011107
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI116382
Pays : United States
Organisme : NIH HHS
ID : T32 OD011147
Pays : United States
Organisme : NIH HHS
ID : P51 OD011106
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
PLoS Negl Trop Dis. 2021 Mar 5;15(3):e0009211
pubmed: 33667230
Nat Commun. 2016 Jun 28;7:12204
pubmed: 27352279
Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):7981-7989
pubmed: 32209664
J Toxicol Pathol. 2012 Mar;25(1):63-101
pubmed: 22481861
Bull World Health Organ. 2017 Dec 01;95(12):802-809
pubmed: 29200521
PLoS Negl Trop Dis. 2016 Dec 2;10(12):e0005168
pubmed: 27911897
Asian J Androl. 2015 Sep-Oct;17(5):756-63
pubmed: 26112484
EBioMedicine. 2016 Dec;14:112-122
pubmed: 27884655
JAMA. 2014 Aug 6;312(5):562
pubmed: 25096708
Sci Rep. 2018 Oct 18;8(1):15379
pubmed: 30337585
Lancet. 2016 Jun 18;387(10037):2501
pubmed: 27287833
Am J Pathol. 2018 Apr;188(4):904-915
pubmed: 29378173
Nature. 2016 Dec 15;540(7633):438-442
pubmed: 27798603
Rev Inst Med Trop Sao Paulo. 2018 Oct 25;60:e64
pubmed: 30379231
Curr Opin Urol. 2017 Mar;27(2):99-106
pubmed: 27906778
J Infect Dis. 2020 Apr 7;221(9):1506-1517
pubmed: 31616920
Sci Rep. 2020 Aug 3;10(1):13069
pubmed: 32747639
Semin Cell Dev Biol. 2016 Nov;59:157-165
pubmed: 26805443
Cell. 2016 Dec 1;167(6):1511-1524.e10
pubmed: 27884405
Lancet Infect Dis. 2016 Oct;16(10):1107
pubmed: 27676342
Cell Rep. 2018 Nov 6;25(6):1385-1394.e7
pubmed: 30403995
Arch Androl. 1984;12 Suppl:43-51
pubmed: 6535454
PLoS Pathog. 2017 Mar 9;13(3):e1006219
pubmed: 28278237
mBio. 2019 Jul 16;10(4):
pubmed: 31311882
Front Cell Infect Microbiol. 2017 Jun 21;7:272
pubmed: 28680856
Nat Med. 2016 Dec;22(12):1448-1455
pubmed: 27694931
Lancet Infect Dis. 2017 Nov;17(11):1200-1208
pubmed: 28838639
Euro Surveill. 2016 Aug 11;21(32):
pubmed: 27541989
J Infect Dis. 2018 Jan 30;217(4):538-547
pubmed: 28968863
BMC Infect Dis. 2017 Jan 10;17(1):55
pubmed: 28068904
J Clin Invest. 2018 Oct 1;128(10):4697-4710
pubmed: 30063220
Travel Med Infect Dis. 2016 Jul-Aug;14(4):313-30
pubmed: 27425793
Methods Mol Biol. 2013;927:385-96
pubmed: 22992930
Sci Adv. 2017 Feb 22;3(2):e1602899
pubmed: 28261663
N Engl J Med. 2018 Apr 12;378(15):1377-1385
pubmed: 29641964
Cell Rep. 2017 Feb 14;18(7):1751-1760
pubmed: 28199846
N Engl J Med. 2019 Oct 10;381(15):1444-1457
pubmed: 31597021
Euro Surveill. 2016 Aug 11;21(32):
pubmed: 27542178
Antiviral Res. 2016 Jun;130:69-80
pubmed: 26996139
PLoS Negl Trop Dis. 2018 Aug 2;12(8):e0006691
pubmed: 30070988
Nat Commun. 2018 Jun 20;9(1):2414
pubmed: 29925843
Emerg Infect Dis. 2017 Aug;23(8):1274-1281
pubmed: 28548637
Emerg Microbes Infect. 2018 May 9;7(1):82
pubmed: 29739931
Nat Rev Urol. 2019 Apr;16(4):211-230
pubmed: 30696994
Nat Commun. 2018 May 29;9(1):2090
pubmed: 29844387
Fertil Res Pract. 2019 Jan 03;5:1
pubmed: 30619616
PLoS Pathog. 2018 Mar 28;14(3):e1006964
pubmed: 29590202
Prostate. 2008 Oct 1;68(14):1546-54
pubmed: 18668524
PLoS One. 2017 Jan 31;12(1):e0171148
pubmed: 28141843
Viruses. 2019 Jan 09;11(1):
pubmed: 30634400
Clin Microbiol Infect. 2017 May;23(5):296-305
pubmed: 28062314
Toxicol Pathol. 2012 Aug;40(6):935-42
pubmed: 22609951
Toxicol Pathol. 2007 Apr;35(3):395-404
pubmed: 17455088
Regul Toxicol Pharmacol. 2012 Aug;63(3):391-400
pubmed: 22579626
Front Microbiol. 2016 Dec 19;7:2028
pubmed: 28066354
Sci Rep. 2018 Apr 3;8(1):5477
pubmed: 29615760
J Virol. 2017 Oct 27;91(22):
pubmed: 28878076
J Mol Diagn. 2012 Jan;14(1):22-9
pubmed: 22166544
Lancet Infect Dis. 2016 Oct;16(10):1106-1107
pubmed: 27676340
Semin Reprod Med. 2016 Sep;34(5):285-292
pubmed: 27627657
Viruses. 2018 Apr 16;10(4):
pubmed: 29659541
J Infect Dis. 2017 Dec 16;216(suppl_10):S928-S934
pubmed: 29267926