Soluble forms of CD46 are detected in Bos taurus plasma and neutralize BVDV, the bovine pestivirus

Alzamel, Nidal; Bayrou, Calixte; Decreux, Annabelle; Desmecht, Daniël

doi:10.1016/j.cimid.2016.09.001

Cited by 5 publications

(4 citation statements)

References 33 publications

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“…The importance of bovine CD46 for pestivirus entry into a host cell has been already described in detail in the past and the two peptide domains E 66 QIV 69 and G 82 QVLAL 87 have been identified to be crucial [25,34,35]. However, for further analysis, bovine CD46-knock-out cells were needed.…”

Section: Discussionmentioning

confidence: 99%

A CRISPR/Cas9 Generated Bovine CD46-knockout Cell Line—A Tool to Elucidate the Adaptability of Bovine Viral Diarrhea Viruses (BVDV)

Szillat

Koethe

Wernike

et al. 2020

Viruses

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Bovine viral diarrhea virus (BVDV) entry into a host cell is mediated by the interaction of the viral glycoprotein E2 with the cellular transmembrane CD46 receptor. In this study, we generated a stable Madin–Darby Bovine Kidney (MDBK) CD46-knockout cell line to study the ability of different pestivirus A and B species (BVDV-1 and -2) to escape CD46-dependent cell entry. Four different BVDV-1/2 isolates showed a clearly reduced infection rate after inoculation of the knockout cells. However, after further passaging starting from the remaining virus foci on the knockout cell line, all tested virus isolates were able to escape CD46-dependency and grew despite the lack of the entry receptor. Whole-genome sequencing of the escape-isolates suggests that the genetic basis for the observed shift in infectivity is an amino acid substitution of an uncharged (glycine/asparagine) for a charged amino acid (arginine/lysine) at position 479 in the ERNS in three of the four isolates tested. In the fourth isolate, the exchange of a cysteine at position 441 in the ERNS resulted in a loss of ERNS dimerization that is likely to influence viral cell-to-cell spread. In general, the CD46-knockout cell line is a useful tool to analyze the role of CD46 for pestivirus replication and the virus–receptor interaction.

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Section: Discussionmentioning

confidence: 99%

A CRISPR/Cas9 Generated Bovine CD46-knockout Cell Line—A Tool to Elucidate the Adaptability of Bovine Viral Diarrhea Viruses (BVDV)

Szillat

Koethe

Wernike

et al. 2020

Viruses

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“…In InDels, the immune response-related genes were only enriched in WS cattle. Among them, CD46, a type 1 transmembrane glycoprotein, whose main function is to regulate complement activation [32]. We found 55 InDels related to the CD46 gene in WS cattle, suggesting that WS cattle may have well antiviral infection characteristics [33,34].…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide SNPs and InDels Characteristics of Three Chinese Cattle Breeds

Zhang

Chen

et al. 2019

Animals

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Simple SummaryWhole-genome resequencing is an important tool to reveal the in-depth genomic characteristics of a genome. Adaptability traits are key to the survival of the south Chinese zebu cattle. However, the potential genetic information behind these remarkable traits still remains uncertain and needs to be addressed. In the current study, we utilized a total of 15 local south Chinese cattle samples (Leiqiong (LQ), Wannan (WN), Wenshan (WS)) from one of our previous studies mapped to the old reference genome (Btau_5.0.1) and remapped them to the latest reference genome (ARS-UCD1.2) to explore potential single nucleotide polymorphisms (SNPs) and insertions-deletions (InDels) responsible for some important immune related traits. The present study emphasizes and illustrates the genetic diversity, extending our previous study. The InDel annotation show that WS cattle had more enriched genes associated with immune functions than the other two breeds. Our findings provide valuable resources for further investigation of the functions of SNP- and InDels-related genes and help to determine the molecular basis of adaptive mutations in Chinese zebu cattle.AbstractWe report genome characterization of three native Chinese cattle breeds discovering ~34.3 M SNPs and ~3.8 M InDels using whole genome resequencing. On average, 10.4 M SNPs were shared amongst the three cattle breeds, whereas, 3.0 M, 4.9 M and 5.8 M were specific to LQ, WN and WS breeds, respectively. Gene ontology (GO)analysis revealed four immune response-related GO terms were over represented in all samples, while two immune signaling pathways were significantly over-represented in WS cattle. Altogether, we found immune related genes (PGLYRP2, ROMO1, FYB2, CD46, TSC1) in the three cattle breeds. Our study provides insights into the genetic basis of Chinese indicine adaptation to the tropic and subtropical environment, and provides a valuable resource for further investigations of genetic characteristics of the three breeds.

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“…A soluble form of CD46 which neutralizes BVDV in vitro is present in adult bovine plasma and may play a role in viral clearance in postnatal acute infections. However, soluble CD46 is not found in fetal or neonatal serum, and is therefore unlikely to impact PI fetal BVDV infections [62].…”

Section: Pi Thymus and Spleen Exhibit Diminished Or Inhibited Immune mentioning

confidence: 97%

Fetal Lymphoid Organ Immune Responses to Transient and Persistent Infection with Bovine Viral Diarrhea Virus

Knapek

Georges

Campen

et al. 2020

Viruses

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Bovine Viral Diarrhea Virus (BVDV) fetal infections occur in two forms; persistent infection (PI) or transient infection (TI), depending on what stage of gestation the fetus is infected. Examination of lymphoid organs from both PI and TI fetuses reveals drastically different fetal responses, dependent upon the developmental stage of the fetal immune system. Total RNA was extracted from the thymuses and spleens of uninfected control, PI, and TI fetuses collected on day 190 of gestation to test the hypothesis that BVDV infection impairs the innate and adaptive immune response in the fetal thymus and spleen of both infection types. Transcripts of genes representing the innate immune response and adaptive immune response genes were assayed by Reverse Transcription quatitative PCR (RT-qPCR) (2−ΔΔCq; fold change). Genes of the innate immune response, interferon (IFN) inducible genes, antigen presentation to lymphocytes, and activation of B cells were downregulated in day 190 fetal PI thymuses compared to controls. In contrast, innate immune response genes were upregulated in TI fetal thymuses compared to controls and tended to be upregulated in TI fetal spleens. Genes associated with the innate immune system were not different in PI fetal spleens; however, adaptive immune system genes were downregulated, indicating that PI fetal BVDV infection has profound inhibitory effects on the expression of genes involved in the innate and adaptive immune response. The downregulation of these genes in lymphocytes and antigen-presenting cells in the developing thymus and spleen may explain the incomplete clearance of BVDV and the persistence of the virus in PI animals while the upregulation of the TI innate immune response indicates a more mature immune system, able to clear the virus.

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Soluble forms of CD46 are detected in Bos taurus plasma and neutralize BVDV, the bovine pestivirus

Cited by 5 publications

References 33 publications

A CRISPR/Cas9 Generated Bovine CD46-knockout Cell Line—A Tool to Elucidate the Adaptability of Bovine Viral Diarrhea Viruses (BVDV)

A CRISPR/Cas9 Generated Bovine CD46-knockout Cell Line—A Tool to Elucidate the Adaptability of Bovine Viral Diarrhea Viruses (BVDV)

Genome-Wide SNPs and InDels Characteristics of Three Chinese Cattle Breeds

Fetal Lymphoid Organ Immune Responses to Transient and Persistent Infection with Bovine Viral Diarrhea Virus

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