Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection.
PLoS Pathog
; 19(3): e1010843, 2023 03.
Article
em En
| MEDLINE
| ID: mdl-36897927
ABSTRACT
The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNÉ) 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, ß and λ. We show the necessity of IFNÉ for Zika Virus (ZIKV) protection by increased susceptibility of IFNÉ-/- mice; their "rescue" by intravaginal recombinant IFNÉ treatment and blockade of protective endogenous IFNÉ by neutralising antibody. Complementary studies in human FRT cell lines showed IFNÉ had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNÉ 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 IFNÉ expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNß or λ. Thus, the constitutive expression of IFNÉ 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Zika virus
/
Infecção por Zika virus
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Austrália