Identification of a Locus in Mice that Regulates the Collateral Damage and Lethality of Virus Infection
| Autor: | Makayla M. Lund, Joseph E. Mitchell, Fernando Pardo-Manuel de Villena, Robert H. Lee, Wolfgang Bergmeier, Kevin D. Cook, Toru Uchimura, Piotr A. Mieczkowski, Jenny P.-Y. Ting, Jason K. Whitmire, Sarah C. Vick, Ichiro Misumi |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Multiple Organ Failure Viral pathogenesis viruses ComputingMethodologies_IMAGEPROCESSINGANDCOMPUTERVISION Congenic Locus (genetics) Lymphocytic Choriomeningitis Lymphocytic choriomeningitis Article Chromosomes General Biochemistry Genetics and Molecular Biology Virus Cell Line Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Immune system Cricetinae Chlorocebus aethiops medicine Animals Lymphocytic choriomeningitis virus Genetic Predisposition to Disease Vero Cells lcsh:QH301-705.5 ComputingMilieux_MISCELLANEOUS Cells Cultured Arenavirus biology medicine.disease biology.organism_classification Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) Genetic Loci Immunology ComputingMethodologies_DOCUMENTANDTEXTPROCESSING Female 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 27, Iss 5, Pp 1387-1396.e5 (2019) |
| ISSN: | 2211-1247 |
| Popis: | Summary: Arenaviruses can cause severe hemorrhagic disease in humans, which can progress to organ failure and death. The underlying mechanisms causing lethality and person-to-person variation in outcome remain incompletely explained. Herein, we characterize a mouse model that recapitulates many features of pathogenesis observed in humans with arenavirus-induced hemorrhagic disease, including thrombocytopenia, severe vascular leakage, lung edema, and lethality. The susceptibility of congenic B6.PL mice to lymphocytic choriomeningitis virus (LCMV) infection is associated with increased antiviral T cell responses in B6.PL mice compared with C57BL/6 mice and is T cell dependent. Pathogenesis imparted by the causative locus is inherited in a semi-dominant manner in F1 crosses. The locus includes PL-derived sequence variants in both poorly annotated genes and genes known to contribute to immune responses. This model can be used to further interrogate how limited genetic differences in the host can remarkably alter the disease course of viral infection. : Arenaviruses can cause devastating illness, including severe systemic hemorrhaging and death in humans. Misumi et al. characterize a mouse model that recapitulates many features of pathogenesis observed in humans and identify a genetic locus that regulates T cell responses, platelet frequencies, and pathogenesis during arenavirus infection. Keywords: viral hemorrhagic disease, viral pathogenesis, arenavirus, LCMV, mouse genetics, forward genetic mapping, CD8+ T cells, thrombocytopenia |
| Databáze: | OpenAIRE |
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