OBJECTIVES: In order to evaluate the association between the Hantaan virus-induced cellular-immune response and clinical severity in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: We serially measured the serum (n = 16) and urine (n = 6) concentrations of soluble HLA class 1 antigen (sHLA-l) and clinical powameters in patients with HFRS. RESULTS: Serum sHLA-I concentrations in patients with HFRS were significantly higher than those in controls throughout all clinical phases (p < 0.01). The highly elevated Serum sHLA-I concentrations peaked in the oliguric phase and declined gradually through the phases of HFRS. Serum sHLA-l concentrations in patients with hypotensive episode were higher than in those without the episode (5,85 +/-2,184 vs. 2,389 +/- 860 ng/ml in oliguric phase, 4.11 +/- 1,952 vs. 1,502 +/- 592 ng/ml in diuretic phase, p < 0.05), and serum sHLA-l levels showed a significant correlation with blood WBC count (r = 0.75 in the febrile and hypotensive phase, p < 0.01) and serum creatinine concentrations (r = 0.64 in the oliguric phase, p< 0.01), respectively, Urine sHLA-I levels in the oliguric phase were significantly higher than those in the diuretic phase (390 +/- 155 vs. 214 +/- 45 ng/mg Cr, p < 0.05) and urine sHLA-I levels are associated with severe illness in patients with HFRS. The higher serum sHLA-I are associated with severe illness in patients with HFRS. The persistent elevation of serum sHLA-I during all phases of HFRS might be related to increased production due to prolonged cellular immunologic stimulation by the Hantaan virus rather than decreased excretion of sHLA-I through the kidney. CONCLUSION: We suggest that the serum and urine sHLA-I concentrations can be used as a stable and objective parameter for monitoring clinical severity and renal dysfunction in patients with HFRS.
Adult ; Enzyme-Linked Immunosorbent Assay ; HLA-A Antigens/urine* ; HLA-A Antigens/blood* ; Hemorrhagic Fever with Renal Syndrome/physiopathology ; Hemorrhagic Fever with Renal Syndrome/immunology* ; Human ; Male ; Sensitivity and Specificity ; Severity of Illness Index

Hantaan virus ; genetics ; isolation & purification ; Hemorrhagic Fever with Renal Syndrome ; prevention & control ; virology ; Humans ; Viral Vaccines ; immunology

Hemorrhagic Fever with Renal Syndrome ; immunology ; prevention & control ; Humans ; Viral Vaccines ; isolation & purification ; therapeutic use

Animals ; Antibodies, Viral ; analysis ; immunology ; Hemorrhagic Fever with Renal Syndrome ; diagnosis ; immunology ; prevention & control ; Humans ; Periodicals as Topic ; Vaccination

The purpose of this study is to delineate the histopathologic findings of the spleen after Hantaan viral inoculation, which is the largest lymphoid organ in rats, and to identify the viral location by anti-Hantaan virus (HTNV) monoclonal antibody. All the sixty one suckling rats of less than twenty four hours of age were used. Except twenty one rats of control group, twenty-five rats inoculated intracerebrally for the early change and fifteen suckling rats inoculated intramuscularly for the late change were uniformly susceptible to lethal infection with the ROK 84-105-1 strain of seed HTNV. The characteristic histopathologic findings were; appearance of macrophages below the splenic capsule on the 3rd day, small lymphocytes around the periarteriolar sheath on the 5th day increasing in numbers on the 7th day, and a markedly expanded marginal zone with some immunoblasts and plasma cells as well as decreased extramedullary hematopoiesis on the 9th and 14th days. Time of onset of histopathologic changes in spleen thickness, appearance of medium and large lymphocytes and degree of extramedullary hematopoiesis were influenced by inoculation route, whereas expansion of the marginal zone was affected by postnatal age.
Animals ; Animals, Suckling ; Antigens, Viral/analysis ; Hantavirus/immunology ; Hematopoiesis ; Hemorrhagic Fever with Renal Syndrome/*pathology ; Rats ; Rats, Inbred Strains ; Spleen/*pathology

OBJECTIVETo observe the changes of the plasma pro-inflammatory cytokines levels in patients with hemorrhagic fever with renal syndrome (HFRS).

METHODSEnzyme-linked immunosorbent assay (ELISA) was performed to detect the plasma pro-inflammatory cytokines levels of 22 HFRS patients (9 mild cases and 13 moderate cases) 1, 4, and 12 weeks after they were diagnosed. Sixteen healthy blood donors were recruited as control group.

RESULTSThe levels of interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and IL-8 in HFRS patients were significantly higher than those in control group 1 week after they were diagnosed (all P < 0.01). The levels of IL-6 and TNF-alpha in HFRS patients returned to the normal levels four weeks after the diagnosis, while those of IL-1beta, IL-8, and IL-10 remained significantly higher than those in control group 12 weeks after the diagnosis (all P < 0.01). The IL-8 and IL-10 levels in mild HFRS patients were significantly higher than those in moderate HFRS patients at the same period (all P < 0.05).

CONCLUSIONAbnormal expressions and secretion of pro-inflammatory cytokines occurs during the disease course of HFRS.

Adult ; Animals ; Cytokines ; blood ; Hemorrhagic Fever with Renal Syndrome ; blood ; immunology ; Humans ; Inflammation Mediators ; blood ; Male ; Middle Aged ; Young Adult

OBJECTIVES: In HFRS, there is a varying degree of disseminated intravascular coagulation which was evident in the early phase of the illness. It is believed also that DIC would be the consequence, at least in part, of functional changes of endothelium resulting in kinin activation and clinical syndrome. This study investigated the role of adhesion molecule in the pathogenesis of Hantaan virus-related disease. METHODS: The expression of ICAM-1 antigen on the cell membrane of human umbilical vein endothelial cells was assessed by immunohistochemistry, and ICAM-1 mRNA in the endothelial cells was assessed by in situ hybridization after Hantaan virus infection (2.6 x 10(4) PFU/mL) with the time course. RESULTS: In immunohistochemistry, the number of ICAM-1 positive cells increased with time during the 12 or 24 hours after infection. 5 to 10% of HUVECs had been positive after 12-24 hours and the number of positive cells decreased abruptly after 24 hours. Hantaan antigen had been noticed after 12 hours focally on the HUVECs but continued to proliferate into day 7 post-infection when most of HUVECs were infected by Hantaan virus. In situ hybridization showed identical patterns of ICAM-1 mRNA expression after Hantaan virus infection. CONCLUSION: It implies that the Hantaan virus infection on HUVECs would express more ICAM-1 on their surface and implicated in the pathogenesis of early clinical syndrome of HFRS.
Cell Line ; Endothelium, Vascular/virology ; Endothelium, Vascular/immunology ; Gene Expression ; Hantaan Virus/pathogenicity* ; Hemorrhagic Fever with Renal Syndrome/immunology* ; Hemorrhagic Fever with Renal Syndrome/genetics ; Hemorrhagic Fever with Renal Syndrome/etiology ; Human ; Immunohistochemistry ; In Situ Hybridization ; Intercellular Adhesion Molecule-1/metabolism* ; Intercellular Adhesion Molecule-1/genetics* ; RNA, Messenger/metabolism ; RNA, Messenger/genetics

This is the first case of virus-associated encephalitis/encephalopathy in which the pathogen was Hantaan virus. A 53-yr-old man presented fever, renal failure and a hemorrhagic tendency and he was diagnosed with hemorrhagic fever with renal failure syndrome (HFRS). In the course of his illness, mild neurologic symptoms such as dizziness and confusion developed and magnetic resonance images revealed a reversible lesion in the splenium of the corpus callosum. This case suggests that HFRS patients with neurologic symptoms like dizziness and mental slowing should be considered to have structural brain lesions and to require brain imaging studies.
Antibodies, Viral/blood ; Corpus Callosum/*pathology ; Diagnosis, Differential ; Hantaan virus/immunology ; Hemorrhagic Fever with Renal Syndrome/*diagnosis/therapy ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Platelet Count ; Renal Dialysis

Animals ; China ; epidemiology ; Disease Reservoirs ; Hantaan virus ; immunology ; isolation & purification ; Hemorrhagic Fever with Renal Syndrome ; epidemiology ; prevention & control ; transmission ; Humans ; Prevalence ; Vaccination ; Vaccines, Inactivated ; Viral Vaccines ; immunology

OBJECTIVETo develop a chemiluminescent enzyme-linked immunosorbent assay (CLEIA) for the detection of HTNV IgM antibody.

METHODSBlack solid 96 well microplate was coated with anti-human IgM-microantibody, HRP labeled HTNV recombinant nucleotide antigen was used as detection antigen, luminol-H2O2 was used as substrate, a CLEIA was established for the detection of HFRS patient serum IgM antibody and comparison of detection sensitivity, specificity, and stability were made between CLEIA and MacELISA.

RESULTSCorrelate coefficient of CLEIA with MacELISA is 0.97; detection sensitivity of CLEIA is 100 percent while that of MacELISA is 92.1 percent; detection specificity of CLEIA and MacELISA are both 100 percent; coefficient of variance for intra-assay and inter-assay of CLEIA are both less than 15 percent, which are comparative with MacELISA.

CONCLUSIONThe established method of CLEIA is a sensitive, selective, and stable method; it is suitable for the early detection of HFRS patient serum IgM antibody.

Antibodies, Viral ; blood ; Antibody Specificity ; Enzyme-Linked Immunosorbent Assay ; methods ; Hantavirus ; immunology ; Hemorrhagic Fever with Renal Syndrome ; immunology ; Humans ; Immunoglobulin M ; blood ; Luminescent Measurements ; methods