Bovine Viral Diarrhoea Virus Infection Disrupts Uterine Interferon Stimulated Gene Regulatory Pathways During Pregnancy Recognition in Cows

Cheng, Zhangrui; Brown, Laura E; Wathes, D C

doi:10.3390/v12010001

Cited by 16 publications

(11 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although a multitude of different SARS-CoV-2 features likely account for its high pathogenicity and transmissivity, it has been speculated that the PRRAR loop might contribute to increased COVID-19 severity. Introduction of similar polybasic cleavage sites into avian influenza viruses and human coronaviruses was shown to render them more pathogenic, increasing mortality and viral spread 158,159 . One hypothesis is that acquisition of a PCSK cleavage site would expand the number of cell types that can be directly infected by SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 99%

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Muus

Luecken

Eraslan

et al. 2020

Preprint

251

326

View full text Add to dashboard Cite

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Muus

Luecken

Eraslan

et al. 2020

Preprint

251

326

View full text Add to dashboard Cite

show abstract

“…In the bovine endometrial cells, IFNT treatment significantly stimulated the expression of many important genes in this pathway, including STAT1, STAT2, IRF9, TYK2, etc. However, in the cells infected with ncp BVDV, the IFNT-induced expression of those genes was significantly suppressed (Cheng et al ., 2018). This suggests yet another mechanism through which ncp BVDV infection may disrupt MRP and early pregnancy by suppressing the functions of ISGs in endometrial immunity and development in early pregnancy.…”

Section: Mechanisms Linking Bvdv Infection With Infertility In Cattlementioning

confidence: 99%

Mechanisms linking bovine viral diarrhea virus (BVDV) infection with infertility in cattle

Oguejiofor

Thomas

Cheng

et al. 2019

Anim. Health. Res. Rev.

Self Cite

View full text Add to dashboard Cite

Bovine viral diarrhea virus (BVDV) is an important infectious disease agent that causes significant reproductive and economic losses in the cattle industry worldwide. Although BVDV infection is known to cause poor fertility in cattle, a greater part of the underlying mechanisms particularly associated with early reproductive losses are not clearly understood. Previous studies reported viral compromise of reproductive function in infected bulls. In females, BVDV infection is thought to be capable of killing the oocyte, embryo or fetus directly, or to induce lesions that result in fetal abortion or malformation. BVDV infections may also induce immune dysfunction, and predispose cattle to other diseases that cause poor health and fertility. Other reports also suggested BVDV-induced disruption of the reproductive endocrine system, and a disruption of leukocyte and cytokine functions in the reproductive organs. More recent studies have provided evidence of viral-induced suppression of endometrial innate immunity that may predispose to uterine disease. Furthermore, there is new evidence that BVDV may potentially disrupt the maternal recognition of pregnancy or the immune protection of the conceptus. This review brings together the previous reports with the more recent findings, and attempts to explain some of the mechanisms linking this important virus to infertility in cattle.

show abstract

“…Among these factors, type I interferon stimulated genes (ISGs) are amongst those most upregulated by IFNT (21,24,25) via the STAT1 and STAT2 -IRF signaling pathway (25). ISGs play crucial roles in the establishment of pregnancy via modulation of uterine immunity, stromal remodeling, stimulating hyperplasia of the endometrial glands, and development of the uterine vasculature (23,26,27).…”

Section: Introductionmentioning

confidence: 99%

“…Secondly, IFNT-induced ISG production by the endometrium was also inhibited (24). This inhibition was achieved, at least in part, by suppressing the activation effect of IFNT on the signaling pathways associated with IFNT receptors, JAK1/TYK2, IRFs, STAT1, and STAT2 (25). There is substantial evidence that infection with BVDV is strongly associated with pregnancy failure (32)(33)(34)(35).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Ability of High and Low Virulence Strains of Non-cytopathic Bovine Viral Diarrhea Virus-1 to Modulate Expression of Interferon Tau Stimulated Genes in Bovine Endometrium

et al. 2021

Self Cite

View full text Add to dashboard Cite

Bovine Viral Diarrhea virus (BVDV) is a pestivirus with a single-stranded, positive sense RNA genome. It is endemic in many cattle populations, causing major economic losses in part due to reduced fertility. BVDV exhibits great genetic diversity and is classified as type 1 or 2 (BVDV-1, BVDV-2) with either non-cytopathogenic (ncp) or cytopathogenic (cp) biotypes. Differing strains of ncpBVDV differ in virulence, affecting clinical outcome. BVDV replicates in the reproductive tract, affecting host immunity and embryo survival. This study used an in vitro model of primary bovine endometrial cell cultures to compare the effects of two BVDV ncp type 1a strains of differing virulence (termed HO and KY) on endometrial transcription of candidate interferon stimulated genes (ISG) using qPCR. Half the cultures were stimulated with interferon tau (IFNT, the conceptus produced pregnancy recognition factor) in the presence or absence of viral infection. Cultures were replicated on cells from 10 BVDV-free cows. IFNT treatment stimulated transcription of 10 candidate ISGs, whereas both ncpBVDV-1 strains alone inhibited transcription of 8/10 ISGs. In combined BVDV-1+IFNT cultures, the stimulatory effect of IFNT on expression of GBP4, ISG15, HERC5, RSAD2, IFIH1, IFIT3, and MX1 was significantly inhibited by HO, but only ISG15, RSAD2, IFI27, and IFIT3 were decreased by KY. Inhibition by HO was generally greater. The IFNT-induced expression of TRIM56 was, however, increased by HO. These data show that HO, the more virulent ncpBVDV-1 strain, has a greater capacity to inhibit key antiviral pathways. These differences need confirmation at the protein level but may influence immune tolerance of the host. They could also reduce fertility by increasing uterine susceptibility to bacterial infection and disrupting IFNT-mediated pregnancy recognition.

show abstract

Bovine Viral Diarrhoea Virus Infection Disrupts Uterine Interferon Stimulated Gene Regulatory Pathways During Pregnancy Recognition in Cows

Cited by 16 publications

References 51 publications

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

Mechanisms linking bovine viral diarrhea virus (BVDV) infection with infertility in cattle

Comparison of the Ability of High and Low Virulence Strains of Non-cytopathic Bovine Viral Diarrhea Virus-1 to Modulate Expression of Interferon Tau Stimulated Genes in Bovine Endometrium

Contact Info

Product

Resources

About