Abstract
Gestational age determines the outcome of congenital LCM virus infection in humans: Confirmation in an animal model
Journal of neurovirology, Vol.12(Suppl 1), pp.8-8
05/01/2006
DOI: 10.1080/13550280600770858
Abstract
Lymphocytic choriomeningitis virus (LCMV) can severely damage the human fetal brain. We studied 20 cases of human congenital LCMV and found a wide range of pathology and outcomes among infected infants. We hypothesized that gestational age affects the pathogenesis of LCMV. We tested this hypothesis by infecting neonatal rats on postnatal day (PD) 1,4,6,10,21,30 or 60. Viral titers and pattern of infection were determined on post-inoculation day (PI)14, and neuropathology on PI 25. The pattern of infection depended strongly on the age of the animal. Neurons and glial cells that were readily infectable at one age were no longer infectable at another. For example, cerebral cortical neurons and hippocampal pyramidal cells were readily infectable on PD1, but were no longer targets of infection by PD4. Peak viral titers also changed dramatically based on the age of the host at the time of infection. Over the course of several days, brain infectability fell multiple orders of magnitude. The severity and nature of neuropathology also depended strongly on age. Infection at certain developmental ages interfered with neurogenesis and produced focal brain hypoplasia, while infection at other ages led to an acute inflammatory response and caused tissue destruction. Brain pathology was a function of viral titer and CD8+ T-cell infiltration, both of which varied among brain regions and depended on host age. All of the various pathologic changes in humans with congenital LCMV infection were reproduced in the rat model by altering the age of the animal at the time of infection. Thus, the variation in outcome in human congenital LCMV infection reflects differences in gestational age at the time of infection.
Details
- Title: Subtitle
- Gestational age determines the outcome of congenital LCM virus infection in humans: Confirmation in an animal model
- Creators
- Daniel J Bonthius - University of Iowa, Stead Family Department of PediatricsBahri Karacay - University of Iowa, Stead Family Department of PediatricsJo MahoneyNancy E Bonthius - University of Iowa, Stead Family Department of Pediatrics
- Resource Type
- Abstract
- Publication Details
- Journal of neurovirology, Vol.12(Suppl 1), pp.8-8
- DOI
- 10.1080/13550280600770858
- ISSN
- 1355-0284
- eISSN
- 1538-2443
- Language
- English
- Date published
- 05/01/2006
- Academic Unit
- Iowa Neuroscience Institute; Stead Family Department of Pediatrics; General Pediatrics and Adolescent Medicine
- Record Identifier
- 9984071601202771
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