Classification of fetal resilience to porcine reproductive and respiratory syndrome (PRRS) based on temporal viral load in late gestation maternal tissues and fetuses

Malgarin, Carolina Maciel; Nosach, Roman; Novakovic, Predrag; Suleman, Muhammad; Ladinig, Andrea; Detmer, Susan E.; MacPhee, Daniel J.; Harding, John C. S.

doi:10.1016/j.virusres.2018.12.002

Cited by 23 publications

(32 citation statements)

References 34 publications

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“…Like most mammals, the vital requirement for thyroid hormone in the developing pig fetus was established long ago [12], and as such, the development of an NTIS-like condition would be assumed to have a detrimental impact on development and possibly survival. In addition, previous work utilizing the model has clearly demonstrated a relationship between fetal susceptibility to infection, and fetal size or intrauterine growth retardation status which may be the related to thyroid function [13,14].…”

Section: Introductionmentioning

confidence: 88%

“…Highly infected fetuses in Experiment 1 were selected with a cut off of > 5 log in serum and thymus and in Experiment 2 as > 4.5 log in serum, thymus and placenta, with the decreased threshold to account for shorter viral replication periods when terminated at 12 dpi. The highly infected fetuses from both trials were then subdivided into resilient fetuses [13] that remained VIA despite high viral load (HV-VIA) and susceptible fetuses who exhibited both high viral load and meconium staining (HV-MEC), an early marker of fetal compromise. For reference, a small number of control (CON) fetuses were drawn from the litters of gestation day matched, mock-inoculated gilts.…”

Section: Viral Load and Group Selectionmentioning

confidence: 99%

“…Using the vast sample archive, we investigated (and herein report) the circulating levels of total T4 and T3 in the pregnant gilt following late gestation infection with a well characterized strain of PRRSV2. We then investigated changes in these hormones in fetuses derived from two well characterized, large-scale trials terminating at 12 and 21 days post maternal infection (dpi) [1,13,16]. To determine the association between thyroid hormone disruption and fetal viability, we utilized infection status as determined by viral load in multiple fetal tissues, and meconium staining as a marker of severe fetal pathology and imminent compromise [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection

Pasternak

MacPhee

Harding

2020

Vet Res

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To better understand the host response to porcine reproductive and respiratory virus-2 (PRRSV2) we evaluated circulating thyroid hormone and associated gene expression in a late gestation challenge model. Pregnant gilts were inoculated at gestation day 85 and fetal samples collected at either 12 or 21 days post-infection (dpi). A subset of fetuses was selected for analysis based on viability and viral load categorized as either uninfected-viable (UNIF), high viral load viable (HV-VIA) or high viral load meconium stained (HV-MEC) and were compared with gestational age matched controls (CON). In dams, circulating levels of total T3 and T4 decreased in the acute period following infection and rebounded by 21 dpi. A similar effect was observed in fetuses, but was largely restricted to HV-VIA and HV-MEC, with minimal decrease noted in UNIF relative to CON at 21 dpi. Gene expression in fetal heart at 12 dpi showed significant decompensatory transcription of thyroid hormone transporters (SLC16A2) and deiodinases (DIO2, DIO3), which was not observed in brain. Correspondingly, genes associated with cell cycle progression (CDK1,2,4) were downregulated in only the heart of highly infected fetuses, while expression of their inhibitor (CDKN1A) was upregulated in both tissues. Finally, expression of genes associated with cardiac stress including CAMKD and AGT were upregulated in the hearts of highly infected fetuses, and a shift in expression of MYH6 to MYH7 was observed in HV-MEC fetuses specifically. Collectively, the results suggest PRRSV2 infection causes a hypothyroid state that disproportionally impacts the fetal heart over the brain.

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Section: Introductionmentioning

confidence: 88%

Section: Viral Load and Group Selectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection

Pasternak

MacPhee

Harding

2020

Vet Res

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“…Our current study is part of the largest set of studies to date using the pregnant gilt challenge model to understand phenotypic and genotypic responses to PRRSV infection in fetuses and gilts [ 15 ]. PRRSV was found to be translocated from dam to fetal placenta within 2 DPI, was first found in fetal thymus by 8 DPI, and 73% (36 of 49) of fetuses had detectable virus in their serum by 12 DPI [ 16 ]. Critical questions remain to understand transplacental PRRSV infection, especially the role of tissues at the MFI (e.g., placenta) and immune tissues in the fetus (e.g., the thymus).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, fetuses were grouped by PRRS VL; uninfected (UNINF), virus in the placenta only (PLCO), low viral load (LVL), or high viral load (HVL). The fetal classifications described in the current study are based on previous work in our group [ 16 ]; UNINF, PLCO-VIA, and PLCO-MEC groups are resistant as they have, at least thus far, avoided or minimized infection suggesting some capacity to prevent viral entry/replication [ 17 ]. Fetuses classified as LVL-VIA and HVL-VIA are tolerant/resilient as they remain uncompromised in the face of viral infection [ 18 ], whereas the LVL-MEC and HVL-MEC are considered susceptible as they are neither able to limit viral replication and/or survive it [ 17 ]; fetuses with LVL have better outcomes than those with HVL.…”

Section: Introductionmentioning

confidence: 99%

Differential responses in placenta and fetal thymus at 12 days post infection elucidate mechanisms of viral level and fetal compromise following PRRSV2 infection

et al. 2020

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Background A pregnant gilt infected with porcine reproductive and respiratory syndrome virus (PRRSV) can transmit the virus to her fetuses across the maternal-fetal-interface resulting in varying disease outcomes. However, the mechanisms leading to variation in fetal outcome in response to PRRSV infection are not fully understood. Our objective was to assess targeted immune-related gene expression patterns and pathways in the placenta and fetal thymus to elucidate the molecular mechanisms involved in the resistance/tolerance and susceptibility of fetuses to PRRSV2 infection. Fetuses were grouped by preservation status and PRRS viral load (VL): mock infected control (CTRL), no virus detected (UNINF), virus detected in the placenta only with viable (PLCO-VIA) or meconium-stained fetus (PLCO-MEC), low VL with viable (LVL-VIA) or meconium-stained fetus (LVL-MEC), and high VL with viable (HVL-VIA) or meconium-stained fetus (HVL-MEC). Results The host immune response was initiated only in fetuses with detectable levels of PRRSV. No differentially expressed genes (DEG) in either the placenta or thymus were identified in UNINF, PLCO-VIA, and PLCO-MEC when compared to CTRL fetuses. Upon fetal infection, a set of core responsive IFN-inducible genes (CXCL10, IFIH1, IFIT1, IFIT3, ISG15, and MX1) were strongly upregulated in both tissues. Gene expression in the thymus is a better differentiator of fetal VL; the strong downregulation of several innate and adaptive immune pathways (e.g., B Cell Development) are indicative of HVL. Gene expression in the placenta may be a better differentiator of fetal demise than the thymus, based-on principle component analysis clustering, gene expression patterns, and dysregulation of the Apoptosis and Ubiquitination pathways. Conclusion Our data supports the concept that fetal outcome in response to PRRSV2 infection is determined by fetal, and more significantly placental response, which is initiated only after fetal infection. This conceptual model represents a significant step forward in understanding the mechanisms underpinning fetal susceptibility to the virus.

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Fetal cytokine response to porcine reproductive and respiratory syndrome virus-2 infection

2020

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Classification of fetal resilience to porcine reproductive and respiratory syndrome (PRRS) based on temporal viral load in late gestation maternal tissues and fetuses

Cited by 23 publications

References 34 publications

Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection

Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection

Differential responses in placenta and fetal thymus at 12 days post infection elucidate mechanisms of viral level and fetal compromise following PRRSV2 infection

Fetal cytokine response to porcine reproductive and respiratory syndrome virus-2 infection

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