In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 3 ( 2023-3-10), p. e1010843-
Abstract:
The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNɛ) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, β and λ. We show the necessity of IFNɛ for Zika Virus (ZIKV) protection by: increased susceptibility of IFNɛ -/- mice; their “rescue” by intravaginal recombinant IFNɛ treatment and blockade of protective endogenous IFNɛ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNɛ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNɛ activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNɛ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNβ or λ. Thus, the constitutive expression of IFNɛ provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010843
DOI:
10.1371/journal.ppat.1010843.g001
DOI:
10.1371/journal.ppat.1010843.g002
DOI:
10.1371/journal.ppat.1010843.g003
DOI:
10.1371/journal.ppat.1010843.g004
DOI:
10.1371/journal.ppat.1010843.g005
DOI:
10.1371/journal.ppat.1010843.g006
DOI:
10.1371/journal.ppat.1010843.g007
DOI:
10.1371/journal.ppat.1010843.s001
DOI:
10.1371/journal.ppat.1010843.s002
DOI:
10.1371/journal.ppat.1010843.s003
DOI:
10.1371/journal.ppat.1010843.s004
DOI:
10.1371/journal.ppat.1010843.s005
DOI:
10.1371/journal.ppat.1010843.s006
DOI:
10.1371/journal.ppat.1010843.s007
DOI:
10.1371/journal.ppat.1010843.s008
DOI:
10.1371/journal.ppat.1010843.s009
DOI:
10.1371/journal.ppat.1010843.s010
DOI:
10.1371/journal.ppat.1010843.s011
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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