Oas1b-dependent immune transcriptional profiles of west nile virus infection in the collaborative cross

Richard Green, Courtney Wilkins, Sunil Thomas, Aimee Sekine, Duncan M. Hendrick, Kathleen Voss, Renee C. Ireton, Michael Mooney, Jennifer T. Go, Gabrielle Choonoo, Sophia Jeng, Fernando Pardo Manuel de Villena, Martin T. Ferris, Shannon McWeeney, Michael Gale

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes.

Original languageEnglish (US)
Pages (from-to)1665-1682
Number of pages18
JournalG3: Genes, Genomes, Genetics
Volume7
Issue number6
DOIs
StatePublished - Jun 1 2017

Fingerprint

West Nile virus
Flavivirus Infections
Virus Diseases
Ligases
Spleen
Genes
Gene Expression
Gene Dosage
Brain
Haplotypes
Immunity
Alleles
Proteins
2',5'-oligoadenylate
Genetic Background

Keywords

  • Flavivirus
  • Innate immunity
  • MPP
  • Multi-parent Advanced Generation Inter-Cross (MAGIC)
  • Multiparental populations
  • Oas
  • Viral infection

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Green, R., Wilkins, C., Thomas, S., Sekine, A., Hendrick, D. M., Voss, K., ... Gale, M. (2017). Oas1b-dependent immune transcriptional profiles of west nile virus infection in the collaborative cross. G3: Genes, Genomes, Genetics, 7(6), 1665-1682. https://doi.org/10.1534/g3.117.041624

Oas1b-dependent immune transcriptional profiles of west nile virus infection in the collaborative cross. / Green, Richard; Wilkins, Courtney; Thomas, Sunil; Sekine, Aimee; Hendrick, Duncan M.; Voss, Kathleen; Ireton, Renee C.; Mooney, Michael; Go, Jennifer T.; Choonoo, Gabrielle; Jeng, Sophia; de Villena, Fernando Pardo Manuel; Ferris, Martin T.; McWeeney, Shannon; Gale, Michael.

In: G3: Genes, Genomes, Genetics, Vol. 7, No. 6, 01.06.2017, p. 1665-1682.

Research output: Contribution to journalArticle

Green, R, Wilkins, C, Thomas, S, Sekine, A, Hendrick, DM, Voss, K, Ireton, RC, Mooney, M, Go, JT, Choonoo, G, Jeng, S, de Villena, FPM, Ferris, MT, McWeeney, S & Gale, M 2017, 'Oas1b-dependent immune transcriptional profiles of west nile virus infection in the collaborative cross', G3: Genes, Genomes, Genetics, vol. 7, no. 6, pp. 1665-1682. https://doi.org/10.1534/g3.117.041624
Green, Richard ; Wilkins, Courtney ; Thomas, Sunil ; Sekine, Aimee ; Hendrick, Duncan M. ; Voss, Kathleen ; Ireton, Renee C. ; Mooney, Michael ; Go, Jennifer T. ; Choonoo, Gabrielle ; Jeng, Sophia ; de Villena, Fernando Pardo Manuel ; Ferris, Martin T. ; McWeeney, Shannon ; Gale, Michael. / Oas1b-dependent immune transcriptional profiles of west nile virus infection in the collaborative cross. In: G3: Genes, Genomes, Genetics. 2017 ; Vol. 7, No. 6. pp. 1665-1682.
@article{ec819d21f35e443e91685369b7d49e2d,
title = "Oas1b-dependent immune transcriptional profiles of west nile virus infection in the collaborative cross",
abstract = "The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes.",
keywords = "Flavivirus, Innate immunity, MPP, Multi-parent Advanced Generation Inter-Cross (MAGIC), Multiparental populations, Oas, Viral infection",
author = "Richard Green and Courtney Wilkins and Sunil Thomas and Aimee Sekine and Hendrick, {Duncan M.} and Kathleen Voss and Ireton, {Renee C.} and Michael Mooney and Go, {Jennifer T.} and Gabrielle Choonoo and Sophia Jeng and {de Villena}, {Fernando Pardo Manuel} and Ferris, {Martin T.} and Shannon McWeeney and Michael Gale",
year = "2017",
month = "6",
day = "1",
doi = "10.1534/g3.117.041624",
language = "English (US)",
volume = "7",
pages = "1665--1682",
journal = "G3: Genes, Genomes, Genetics",
issn = "2160-1836",
publisher = "Genetics Society of America",
number = "6",

}

TY - JOUR

T1 - Oas1b-dependent immune transcriptional profiles of west nile virus infection in the collaborative cross

AU - Green, Richard

AU - Wilkins, Courtney

AU - Thomas, Sunil

AU - Sekine, Aimee

AU - Hendrick, Duncan M.

AU - Voss, Kathleen

AU - Ireton, Renee C.

AU - Mooney, Michael

AU - Go, Jennifer T.

AU - Choonoo, Gabrielle

AU - Jeng, Sophia

AU - de Villena, Fernando Pardo Manuel

AU - Ferris, Martin T.

AU - McWeeney, Shannon

AU - Gale, Michael

PY - 2017/6/1

Y1 - 2017/6/1

N2 - The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes.

AB - The oligoadenylate-synthetase (Oas) gene locus provides innate immune resistance to virus infection. In mouse models, variation in the Oas1b gene influences host susceptibility to flavivirus infection. However, the impact of Oas variation on overall innate immune programming and global gene expression among tissues and in different genetic backgrounds has not been defined. We examined how Oas1b acts in spleen and brain tissue to limit West Nile virus (WNV) susceptibility and disease across a range of genetic backgrounds. The laboratory founder strains of the mouse Collaborative Cross (CC) (A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, and NZO/HlLtJ) all encode a truncated, defective Oas1b, whereas the three wild-derived inbred founder strains (CAST/EiJ, PWK/PhJ, and WSB/EiJ) encode a full-length OAS1B protein. We assessed disease profiles and transcriptional signatures of F1 hybrids derived from these founder strains. F1 hybrids included wild-type Oas1b (F/F), homozygous null Oas1b (N/N), and heterozygous offspring of both parental combinations (F/N and N/F). These mice were challenged with WNV, and brain and spleen samples were harvested for global gene expression analysis. We found that the Oas1b haplotype played a role in WNV susceptibility and disease metrics, but the presence of a functional Oas1b allele in heterozygous offspring did not absolutely predict protection against disease. Our results indicate that Oas1b status as wild-type or truncated, and overall Oas1b gene dosage, link with novel innate immune gene signatures that impact specific biological pathways for the control of flavivirus infection and immunity through both Oas1b-dependent and independent processes.

KW - Flavivirus

KW - Innate immunity

KW - MPP

KW - Multi-parent Advanced Generation Inter-Cross (MAGIC)

KW - Multiparental populations

KW - Oas

KW - Viral infection

UR - http://www.scopus.com/inward/record.url?scp=85020295478&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020295478&partnerID=8YFLogxK

U2 - 10.1534/g3.117.041624

DO - 10.1534/g3.117.041624

M3 - Article

C2 - 28592649

AN - SCOPUS:85020295478

VL - 7

SP - 1665

EP - 1682

JO - G3: Genes, Genomes, Genetics

JF - G3: Genes, Genomes, Genetics

SN - 2160-1836

IS - 6

ER -