Pathogenesis of cerebral infarction and hemorrhage induced by a murine leukemia virus.
BACKGROUND
Inoculation of neonatal BALB/c mice with the Friend murine leukemia virus TR1.3 uniformly induces cerebral infarctions and hemorrhages within 18 days. The primary target of TR1.3 infection are endothelial cells of capillaries and small vessels. Preliminary post-mortem histologic analysis revealed multifocal endothelial cell pathology associated with the presence of thrombi and extravasation of red blood cells into the brain parenchyma. The consequences of viral infection on endothelial cell integrity and its relevance to hemorrhagic and ischemic lesions are unclear.


METHODS
Neonatal BALB/c mice were infected with TR1.3 murine leukemia virus and were monitored daily for symptoms of tremor, seizure and paralysis. Diseased mice were killed and the brains prepared for histopathologic analysis and electron microscopy studies.


RESULTS
Hematoxylin and eosin-stained sections revealed widespread areas of infarction throughout white and grey matter with numerous scattered thrombi. Endothelial cell pathology was widespread and pronounced. This included enlarged cytoplasm, intracytoplasmic clefts, separation of tight junctions, swollen mitochondria, changes to the basal lamina and in many instances the formation of syncytia. Ultrastructural studies identified numerous viral particles within the endothelial cell cytoplasm and budding from the abluminal and luminal cell surfaces.


CONCLUSIONS
These data confirm that TR1.3 virus replicates within endothelial cells and provides the first direct evidence of retrovirus-induced endothelial cell pathology. These results suggest that hemorrhage may be a direct consequence of this endothelial cell pathology, and that endothelial cell damage initiates the formation of thrombi and vessel occlusion that results in multiple cerebral infarctions.
Park
B H
BH
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia.
Lavi
E
E
Stieber
A
A
Gaulton
G N
GN
D000818:Animals; D002543:Cerebral Hemorrhage / Q000382:microbiology* / Q000473:pathology; D002544:Cerebral Infarction / Q000382:microbiology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D009052:Leukemia Virus, Murine / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D011247:Pregnancy; D012192:Retroviridae Infections / Q000150:complications*; D013927:Thrombosis / Q000150:complications / Q000473:pathology