Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three calves (Nos. 1, 2 = 7 days old; No. 3 = 21 days old) were inoculated subcutaneously with virulent Rift Valley fever (RVF) virus. All calves became viremic and clinically ill, but the two 7-day-old calves were moribund and were euthanatized subsequently on post-inoculation day (PID) 3. Highest viral titers were measured in the serum, with lesser concentrations in the brain, heart, spleen, and liver of these animals. Viral antigens were detected by immunohistochemical analysis only in the livers, where positive staining was localized in coalescing foci of hepatocellular necrosis. The 21-day-old calf appeared to recover after viremia and pyrexia but became lethargic and ataxic and was euthanatized on PID 9. The calf was no longer viremic, and RVF virus was isolated only from the brain. Microscopic examination of the central nervous system revealed diffuse perivascular infiltrates of lymphocytes and macrophages, multifocal meningitis, and focal areas of neuronal necrosis and aggregates of macrophages, lymphocytes, and neutrophils throughout all regions of the brain and cervical spinal cord. There was positive immunohistochemical staining for viral antigens within the cytoplasm of neurons and glial cells throughout the central nervous system. Thus, RVF virus can cause encephalomyelitis in calves, and the specific virologic diagnosis can be made by immunohistochemical localization of viral antigens in formalin-fixed tissues.
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PMID:Rift Valley fever virus-induced encephalomyelitis and hepatitis in calves. 144 95

Rift Valley fever virus is a significant human and veterinary pathogen responsible for explosive outbreaks throughout Africa and the Arabian Peninsula. Severe acute disease in humans includes rapid onset hepatic disease and hemorrhagic fever or delayed onset encephalitis. A highly efficient reverse genetics system was developed which allowed generation of recombinant RVF viruses to assess the role of NSm protein in virulence in a rat model in which wild-type RVF virus strain ZH501 (wt-ZH501) results in 100% lethal hepatic disease 2-3 days post infection. While extensive genomic analysis indicates conservation of the NSm coding capability of diverse RVF viruses, and viruses deficient in NSs proteins are completely attenuated in vivo, comparison of wt-ZH501, a reverse genetics generated wt-ZH501 virus (R-ZH501), and R-ZH501 virus lacking the NSm proteins (R-DeltaNSm-ZH501) demonstrated that the NSm proteins were nonessential for in vivo virulence and lethality. Surprisingly, while 44% of R-DeltaNSm-ZH501 infected animals quickly developed lethal hepatic disease similar to wt- and R-ZH501, 17% developed delayed onset neurologic disease (lethargy, head tremors, and ataxia) at 13 days post infection. Such infections may provide the basis for study of both RVF acute hepatic disease and delayed onset encephalitic disease in humans.
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PMID:Rift Valley fever virus lacking NSm proteins retains high virulence in vivo and may provide a model of human delayed onset neurologic disease. 1741 86