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Early Pathogenesis of Wesselsbron Disease in Pregnant Ewes.

ABSTRACT: Wesselsbron virus (WSLV) is a neglected, mosquito-borne flavivirus that is endemic to the African continent. The virus is teratogenic to ruminants and causes a self-limiting febrile illness in humans. Wesselsbron disease manifests with similar clinical signs and occurs in the same areas under the same climatic conditions as Rift Valley fever, which is therefore included in the differential diagnosis. Although the gross pathology of WSLV infection in pregnant ewes is reported in literature, the pathogenesis that leads to stillbirths, congenital malformations and abortion has remained undescribed. In the present study, pregnant ewes were inoculated with WSLV and subjected to detailed clinical- and histopathology 8 days later. The virus was mainly detected in foetal trophoblasts of the placenta and in neural progenitor cells, differentiated neurons, oligodendrocytes, microglia and astrocytes. Our study demonstrates that WSLV efficiently crosses the maternal-foetal interface and is highly neuroinvasive in the ovine foetus.

SUBMITTER: Oymans J

PROVIDER: S-EPMC7281025 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Early Pathogenesis of Wesselsbron Disease in Pregnant Ewes.

Oymans Judith J van Keulen Lucien L Wichgers Schreur Paul J PJ Kortekaas Jeroen J

Pathogens (Basel, Switzerland) 20200513 5

Wesselsbron virus (WSLV) is a neglected, mosquito-borne flavivirus that is endemic to the African continent. The virus is teratogenic to ruminants and causes a self-limiting febrile illness in humans. Wesselsbron disease manifests with similar clinical signs and occurs in the same areas under the same climatic conditions as Rift Valley fever, which is therefore included in the differential diagnosis. Although the gross pathology of WSLV infection in pregnant ewes is reported in literature, the p ...[more]

PMID: 32414152

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Project description:Modulation of the immune system is known to be important for successful pregnancy but how immune function might differ between the lymph nodes draining the reproductive tract and peripheral lymph nodes is not well understood. Additionally, if immune system changes in response to the presence of an embryo during early pregnancy, and if this response differs in local versus peripheral immune tissue, has not been well characterized. To address these questions, we examined expression of genes important for immune function using NanoString technology in the ampulla and isthmus of the oviduct, endometrium, lymph nodes draining the reproductive tract (lumbo-aortic and medial iliac) as well as a peripheral lymph node (axillary), the spleen, and circulating immune cells from ewes on day 5 of the estrous cycle or pregnancy. Concentrations of estradiol and progesterone in plasma were also determined. Principal component analysis revealed separation of the local from the peripheral lymph nodes (MANOVA P = 3.245e-08, R2 = 0.3) as well as separation of tissues from pregnant and nonpregnant animals [lymph nodes (MANOVA P = 2.337e-09, R2 = 0.5), reproductive tissues (MANOVA P = 2.417e-14, R2 = 0.47)]. Nine genes were differentially (FDR < 0.10) expressed between lymph node types, with clear difference in expression of these genes between the lumbo-aortic and axillary lymph nodes. Expression of these genes in the medial iliac lymph node was not consistently different to either the axillary or the lumbo-aortic lymph node. Expression of IL10RB was increased (FDR < 0.05) by 24% in the reproductive tissue of the pregnant animals compared to nonpregnant animals. Analysis of gene categories revealed that expression of genes of the T-cell receptor pathway in reproductive tract tissues was associated (P < 0.05) with pregnancy status. In conclusion, assessment of gene expression of reproductive and immune tissue provides evidence for a specialization of the local immune system around the reproductive tract potentially important for successful establishment of pregnancy. Additionally, differences in gene expression patterns in reproductive tissue from pregnant and nonpregnant animals could be discerned as early as day 5 of pregnancy. This was found to be associated with expression of genes important for T-cell function and thus highlights the important role of these cells in early pregnancy.

Project description:BACKGROUND: Border disease virus (BDV) causes important reproductive losses, and eradication strategies focus on the identification and removal of persistently infected animals arising after in uterine infection. BDV infection dynamics were studied in 13 ewes experimentally infected with BDV-4 genotype at 3 phases of pregnancy [days 108 (group A), 76 (group B) and 55 (group C)] by quantification of viral RNA in blood collected on days -1 to parturition using quantitative real-time RT-PCR (qRT-PCR). Viral RNA loads were also measured in blood/foetal fluid and tissue samples from their offspring at lambing (3 foetuses, 7 stillborns, 15 lambs). qRT-PCR results were compared with those obtained by conventional RT-PCR and used to predict persistent infections. RESULTS: Viral RNA was detected in the ewes between days 2-15 p.i. The viraemia reached its highest peak between days 6-7 p.i. with a second peak at days 11-12 p.i. qRT-PCR was significantly faster to perform (less than 1 h) than conventional RT-PCR and detected BDV RNA in more ewes, being detection more continuous and prolonged in time. The virus was detected in peripheral blood in a higher percentage of lambs than in tissues, where differences in viral genome copies were more marked. Skin and cerebral cortex showed the highest viral RNA loads, and spleen and spinal cord the lowest. High viral RNA loads were observed in several animals in group B and all in group C, infected during middle and early foetal development, respectively, but also in one lamb from group A, infected during late foetal development. Serology and viral genome copy number estimates in blood and tissues were used to establish a quantitative cut-off threshold for transient viraemia. CONCLUSION: Viral RNA quantification showed potential for the discrimination between persistent infections and transient viraemia using single-time point blood sampling and raised questions regarding foetal immune system development and the occurrence of persistent infections.

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Early Pathogenesis of Wesselsbron Disease in Pregnant Ewes.

Publications

Early Pathogenesis of Wesselsbron Disease in Pregnant Ewes.

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