AgResearch
Browse
- No file added yet -

The response of fetal thymus tissue to infection with a pestivirus

Download (289.63 kB)

Infection of a naive pregnant animal with a pestivirus, such as border disease virus (BDV), during a vulnerable period of pregnancy results in a persistent infection (PI) of the offspring. This persistent infection can have severe negative outcomes for the offspring including reduced weight at birth, reduced growth rate and increased risk of death throughout the animal’s lifetime (fetus through to adult). Multiple systems within the PI animal appear affected including the digestive, immune and reproductive systems. Given the strong interactions between the immune and reproductive systems, our aim was to better understand how infection with the pestivirus affects the developing immune system. Ovine fetuses that were naturally infected with BDV (n=13), as well as contemporary non-infected controls (n=21), were collected on day 50 of gestation. Thymus tissue was collected from the fetuses and expression of various genes associated with immune function, as well as those associated with viral infection, were measured using NanoString. Data were analysed using permutation ANOVA with multiple testing correction performed using the Benjamini-Hochberg (FDR) method with fetus as the experimental unit. Expression of two viral genes, NS2-3 and Polyprotein was increased in infected animals (FDR < 0.001) by 4.8 and 361.6-fold, confirming the infection of the thymus tissue. Several interferon induced genes, including CXCL10, IFIT1, ISG15, MX1, and MX2, were strongly upregulated (FDR < 0.001; 3.2-6.0-fold) in infected fetuses with others, (IFIH1, IRF7) being more moderately upregulated (FDR < 0.05; <2-fold). Other genes differentially expressed (FDR < 0.05; <2.0 fold) included STAT1, NCOA1, OAS1, and PDL1, which were upregulated in infected fetuses compared to their non-infected contemporaries and TNF, ESR2 and FOXP3, which were downregulated. Viral infection of the fetus resulted in activation of the interferon signalling pathway as evidence by upregulation of STAT1 and several interferon induced genes. Given the known role of FOXP3 in regulatory T cell function, down regulation of this gene is consistent with disruption of normal development of the T-regulatory cells.

Funding

MBIE Strategic Science Investment Fund (SSIF)

History

Rights statement

This is an open-access output. It may be used, distributed or reproduced in any medium, provided the original author and source are credited.

Publication date

2023-07-11

Project number

  • PRJ0140125

Language

  • English

Does this contain Māori information or data?

  • No

Publisher

AgResearch Ltd

Conference name

56th Annual Meeting of the Society for the Study of Reproduction (SSR 2023)

Conference location

Ottawa, Canada

Conference start date

2023-07-11

Conference end date

2023-07-14

Usage metrics

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC