Low expression of RNA sensors impacts Zika virus infection in the lower female reproductive tract.
Animals
Female
Gene Expression Regulation, Viral
Genitalia, Female
/ immunology
Humans
Immunity, Innate
/ genetics
Macaca mulatta
Mice, Inbred C57BL
Mice, Knockout
RNA, Viral
/ genetics
Receptor, Interferon alpha-beta
/ genetics
Receptors, Pattern Recognition
/ genetics
Toll-Like Receptor 3
/ genetics
Vagina
/ immunology
Virus Replication
/ genetics
Zika Virus
/ genetics
Zika Virus Infection
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 09 2019
25 09 2019
Historique:
received:
04
03
2019
accepted:
27
08
2019
entrez:
27
9
2019
pubmed:
27
9
2019
medline:
14
1
2020
Statut:
epublish
Résumé
Innate immune responses to Zika virus (ZIKV) are dampened in the lower female reproductive tract (LFRT) compared to other tissues, but the mechanism that underlies this vulnerability is poorly understood. Using tissues from uninfected and vaginally ZIKV-infected macaques and mice, we show that low basal expression of RNA-sensing pattern recognition receptors (PRRs), or their co-receptors, in the LFRT contributes to high viral replication in this tissue. In the LFRT, ZIKV sensing provides limited protection against viral replication, and the sensors are also minimally induced after vaginal infection. While IFNα/β receptor signaling offers minimal protection in the LFRT, it is required to prevent dissemination of ZIKV to other tissues, including the upper FRT. Our findings support a role for RNA-sensing PRRs in the dampened innate immunity against ZIKV in the LFRT compared to other tissues and underlie potential implications for systemic dissemination upon heterosexual transmission of ZIKV in women.
Identifiants
pubmed: 31554802
doi: 10.1038/s41467-019-12371-7
pii: 10.1038/s41467-019-12371-7
pmc: PMC6761111
doi:
Substances chimiques
RNA, Viral
0
Receptors, Pattern Recognition
0
TLR3 protein, mouse
0
Toll-Like Receptor 3
0
Receptor, Interferon alpha-beta
156986-95-7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4344Subventions
Organisme : NIAID NIH HHS
ID : R01 AI097552
Pays : United States
Organisme : NIH HHS
ID : P51 OD011107
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR028962
Pays : United States
Organisme : NIAID NIH HHS
ID : DP2 AI112244
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR)
ID : RR18928
Pays : International
Organisme : NIAID NIH HHS
ID : P30 AI027763
Pays : United States
Organisme : ODCDC CDC HHS
ID : R21 OD023818
Pays : United States
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