Temporal lymphoreticular changes caused by ts1, a paralytogenic mutant of Moloney murine leukemia virus TB.
Inoculation of newborn FVB/N mice with ts1, a mutant of Moloney murine leukemia virus TB, induced severe thymic atrophy, spongiform polioencephalomyelopathy, and fatal posterior paralysis of the affected mice 35-40 days after inoculation. During the early course of infection viral replication was found in the spleen and, more importantly, within the thymus. Of these organs, the thymus was affected most severely by ts1-infection. Thymic weights of infected mice decreased markedly during disease progression, culminating in severe atrophy at the time of paralysis. During the first 10 days after inoculation, the virus replicated within the endothelial lining of splenic and thymic capillaries and was released albuminally into the basement membrane before spreading outwardly into perithelial, epithelial, and reticuloendothelial cells. Within these cells there was productive viral replication and subsequent dissemination of the virus to the thymic T cell population. Early infection (up to 10 days after inoculation) of the thymus induced an increase in thymocytic mitosis, followed by a progressive increase in thymocytic death between 15 and 35 days after inoculation. Thymuses from paralyzed mice killed 30-39 days after inoculation, demonstrated pronounced involution, characterized by loss of lobular architecture, effacement of the cortex and medulla, severe depletion of thymocytes, and partial or complete loss of Hassall's corpuscles. Immunohistochemistry for viral antigens showed positive labeling of splenic megakaryocytes, reticuloendothelial cells, and thymocytes in mitosis, and reticulo-epithelial-endothelial cells of the thymus. The thymic phase of viral replication appeared to be crucial for development of neurological lesions and posterior paralysis.
Stoica
G
G
Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas, A & M University, College Station.
Floyd
E
E
Illanes
O
O
Wong
P K
PK
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy; D004730:Endothelium, Vascular / Q000382:microbiology / Q000473:pathology*; D007942:Leukemia, Experimental / Q000235:genetics / Q000473:pathology*; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D010243:Paralysis; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D013950:Thymus Gland / Q000382:microbiology / Q000473:pathology*; D013997:Time Factors