Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis

ABSTRACT Susceptibility to mouse adenovirus type 1 (MAV-1) is mouse strain dependent; susceptible mice die from hemorrhagic encephalomyelitis. The MAV-1 susceptibility quantitative trait locus Msq1 accounts for ~40% of the phenotypic (brain viral load) variance that occurs between resistant BALB/c a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tien-Huei Hsu, Irene W. Althaus, Oded Foreman, Katherine R. Spindler
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ac1dd438e77841fd8a122f0395f1ac8a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ac1dd438e77841fd8a122f0395f1ac8a
record_format	dspace
spelling	oai:doaj.org-article:ac1dd438e77841fd8a122f0395f1ac8a2021-11-15T15:39:01ZContribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis10.1128/mBio.00131-122150-7511https://doaj.org/article/ac1dd438e77841fd8a122f0395f1ac8a2012-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00131-12https://doaj.org/toc/2150-7511ABSTRACT Susceptibility to mouse adenovirus type 1 (MAV-1) is mouse strain dependent; susceptible mice die from hemorrhagic encephalomyelitis. The MAV-1 susceptibility quantitative trait locus Msq1 accounts for ~40% of the phenotypic (brain viral load) variance that occurs between resistant BALB/c and susceptible SJL mice after MAV-1 infection. Using an interval-specific congenic mouse strain (C.SJL-Msq1SJL), in which the SJL-derived allele Msq1SJL is present in a BALB/c background, we demonstrate that Msq1SJL controls the development of high brain viral titers in response to MAV-1 infection, yet does not account for the total extent of brain pathology or mortality in SJL mice. C.SJL-Msq1SJL mice had disruption of the blood-brain barrier and increased brain water content after MAV-1 infection, but these effects occurred later and were not as severe, respectively, as those noted in infected SJL mice. As expected, BALB/c mice showed minimal pathology in these assays. Infection of SJL- and C.SJL-Msq1SJL-derived primary mouse brain endothelial cells resulted in loss of barrier properties, whereas BALB/c-derived cells retained their barrier properties despite being equally capable of supporting MAV-1 infection. Finally, we provide evidence that organ pathology and inflammatory cell recruitment to the brain following MAV-1 infection were both influenced by Msq1. These results validate Msq1 as an important host factor in MAV-1 infection and refine the major role of the locus in development of MAV-1 encephalitis. They further suggest that additional host factors or gene interactions are involved in the mechanism of pathogenesis in MAV-1-infected SJL mice. IMPORTANCE A successful viral infection requires both host and viral factors; identification of host components involved in viral replication and pathogenesis is important for development of therapeutic interventions. A genetic locus (Msq1) controlling mouse adenovirus type 1 (MAV-1) brain infection was previously identified. Genes in Msq1 belong to the same family of genes associated with susceptibility to other encephalitic viruses, HIV-1 and West Nile virus. We constructed an interval-specific congenic mouse strain to examine the contribution of Msq1 to MAV-1 susceptibility and brain morbidity. We compared infected resistant, susceptible, and congenic mice regarding known MAV-1 disease manifestations in the brain (survival, viral loads, blood-brain barrier disruption, edema, mouse brain endothelial cell barrier properties, pathology, and inflammatory cell recruitment) to determine the extent to which Msq1 influences MAV-1 infection outcome. Our results showed that Msq1 is a critical host genetic factor that controls many aspects of MAV-1 infection.Tien-Huei HsuIrene W. AlthausOded ForemanKatherine R. SpindlerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 3 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Tien-Huei Hsu Irene W. Althaus Oded Foreman Katherine R. Spindler Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis
description	ABSTRACT Susceptibility to mouse adenovirus type 1 (MAV-1) is mouse strain dependent; susceptible mice die from hemorrhagic encephalomyelitis. The MAV-1 susceptibility quantitative trait locus Msq1 accounts for ~40% of the phenotypic (brain viral load) variance that occurs between resistant BALB/c and susceptible SJL mice after MAV-1 infection. Using an interval-specific congenic mouse strain (C.SJL-Msq1SJL), in which the SJL-derived allele Msq1SJL is present in a BALB/c background, we demonstrate that Msq1SJL controls the development of high brain viral titers in response to MAV-1 infection, yet does not account for the total extent of brain pathology or mortality in SJL mice. C.SJL-Msq1SJL mice had disruption of the blood-brain barrier and increased brain water content after MAV-1 infection, but these effects occurred later and were not as severe, respectively, as those noted in infected SJL mice. As expected, BALB/c mice showed minimal pathology in these assays. Infection of SJL- and C.SJL-Msq1SJL-derived primary mouse brain endothelial cells resulted in loss of barrier properties, whereas BALB/c-derived cells retained their barrier properties despite being equally capable of supporting MAV-1 infection. Finally, we provide evidence that organ pathology and inflammatory cell recruitment to the brain following MAV-1 infection were both influenced by Msq1. These results validate Msq1 as an important host factor in MAV-1 infection and refine the major role of the locus in development of MAV-1 encephalitis. They further suggest that additional host factors or gene interactions are involved in the mechanism of pathogenesis in MAV-1-infected SJL mice. IMPORTANCE A successful viral infection requires both host and viral factors; identification of host components involved in viral replication and pathogenesis is important for development of therapeutic interventions. A genetic locus (Msq1) controlling mouse adenovirus type 1 (MAV-1) brain infection was previously identified. Genes in Msq1 belong to the same family of genes associated with susceptibility to other encephalitic viruses, HIV-1 and West Nile virus. We constructed an interval-specific congenic mouse strain to examine the contribution of Msq1 to MAV-1 susceptibility and brain morbidity. We compared infected resistant, susceptible, and congenic mice regarding known MAV-1 disease manifestations in the brain (survival, viral loads, blood-brain barrier disruption, edema, mouse brain endothelial cell barrier properties, pathology, and inflammatory cell recruitment) to determine the extent to which Msq1 influences MAV-1 infection outcome. Our results showed that Msq1 is a critical host genetic factor that controls many aspects of MAV-1 infection.
format	article
author	Tien-Huei Hsu Irene W. Althaus Oded Foreman Katherine R. Spindler
author_facet	Tien-Huei Hsu Irene W. Althaus Oded Foreman Katherine R. Spindler
author_sort	Tien-Huei Hsu
title	Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis
title_short	Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis
title_full	Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis
title_fullStr	Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis
title_full_unstemmed	Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis
title_sort	contribution of a single host genetic locus to mouse adenovirus type 1 infection and encephalitis
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/ac1dd438e77841fd8a122f0395f1ac8a
work_keys_str_mv	AT tienhueihsu contributionofasinglehostgeneticlocustomouseadenovirustype1infectionandencephalitis AT irenewalthaus contributionofasinglehostgeneticlocustomouseadenovirustype1infectionandencephalitis AT odedforeman contributionofasinglehostgeneticlocustomouseadenovirustype1infectionandencephalitis AT katherinerspindler contributionofasinglehostgeneticlocustomouseadenovirustype1infectionandencephalitis
_version_	1718427844169695232

Contribution of a Single Host Genetic Locus to Mouse Adenovirus Type 1 Infection and Encephalitis

Ejemplares similares