A Study On CTL Clone With Specificity Of Hantaan Virus Nucleocapsid Protein From Peripheral Blood Of Patients With HFRS

Hemorrhagic Fever with Renal Syndrome(HFRS) is an acute infectious disease caused by HV infection. It is characterized with high fever, bleeding and kidney damage. Hantaan virus, the prototype member of the Hantavirus genus, causes hemorrhagic fever with renal syndrome(HFRS) in humans. Hantaviruses are carried by rodents and are spread to humans via inhalation of aerosolized virus particles which are shed in the rodent feces and urine. Infections with Hantaan virus can range in severity from asymptomatic to a severe, life-threatening illness characterized by fever, hemorrhage, and renal failure. More than 100,000 cases of HFRS are reported yearly, with a mortality rate of between 2% and 10%. Hantaan-9-virus, which was first isolated in Korea in 1978, is endemic primarily in Asia and causes a relatively severe form of HFRS. Other hantaviruses that also cause HFRS include Dobrava virus(Balkans), Seoul virus(world-wide), and Puumala virus(Scandinavia and Europe). Dobrava virus is also associated with a relatively severe form of HFRS, while Seoul and Puumala viruses cause more mild disease. Recent outbreaks of related hantaviruses in the southwestern United States and South America(e.g., Sin Nombre and Andes viruses) have resulted in the isolation of a newly recognized group of hantaviruses that cause a fatal pulmonary syndrome, hantavirus pulmonary syndrome(HPS). HFRS and HPS are distinct in the predominant target organ of virus infection(kidney versus lung) but have important clinical features in common, including fever, thrombocytopenia, and a capillary leak syndrome. These common clinical manifestations suggest that the underlying mechanisms of disease may be similar in the two syndromes.The pathogenesis of hantavirus infections is not understood. Hantaan virus infects primary human endothelial cells as well as kidney glomerular cells and monocytes in vitro but does not cause any direct cytopathic effect on these cells. It is thus unlikely that direct viral cytotoxicity is the primary cause of pathology in vivo. In many other viral infections, virus-specific cytolytic T-cell responses have been shown to be involved in both clearance of virus and induction of immuno-pathology. This may also be the case in hantavirus infections.An understanding of the mechanisms underlying HFRS pathology will be important both in improving the diagnosis and treatment of infected individuals and in the design of vaccine strategies. Little is known about the specific cellular immune responses to hantavirus infections. In order to elucidate the molecular immunological mechanism and pathogenesis of-10-HFRS, We isolated PBMC from patients with HFRS and established CD8+ cytotoxic T lymphocyte (CTL) clone directly from the peripheral blood mononuclear cells of a patient with the acute hemorrhagic fever with renal syndrome (HFRS). CTL cytotoxic assays were performed as usual using EBV-transformed lymphoblastoid cell lines (BLCL) transfected with HTNV S gene fragments as target cells. Results: The CTL clone recognized and killed the target cells with specificities of HTNV-NP. Conclusion: HTNV T cell antigenic epitopes mainly localized on the C- and N-terminal of the virus nucleocapsid protein. Hantaan virus specific CD8+ CTL may contribute to the immunopathology observed in HFRS...