Hemorrhagic fever with renal syndrome (HFRS) is an acute viral disease with fever, hemorrhage and renal failure caused by hantavirus infection. Hantavirus induces HFRS or hantavirus pulmonary syndrome (HPS). HPS progression to a life-threatening pulmonary disease is found primarily in the USA and very rarely in South Korea. Here, we report a case of HFRS and coexisting HPS.
Fever ; Hantavirus ; Hantavirus Infections ; Hantavirus Pulmonary Syndrome ; Hemorrhage ; Hemorrhagic Fever with Renal Syndrome ; Lung Diseases ; Renal Insufficiency ; Republic of Korea ; Virus Diseases

Hantavirus is known to a causative agent of hemorrhagic fever with renal syndrome and it can cause hantavirus pulmonary syndrome, a rare disease in Korea. Hantavirus pulmonary syndrome is usually associated with pulmonary hemorrhage and fever. The common hematologic features of this syndrome are elevated hematocrit level, leukocytosis and thrombocytopenia. We report a case of hantavirus pulmonary syndrome with pancytopenia. This patient with severe neutropenia with pulmonary infiltration mimicked aplastic anemia with invasive aspergillosis.
Anemia ; Anemia, Aplastic ; Aspergillosis ; Fever ; Hantavirus ; Hantavirus Pulmonary Syndrome ; Hematocrit ; Hemorrhage ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Korea ; Leukocytosis ; Neutropenia ; Pancytopenia ; Rare Diseases ; Thrombocytopenia

Hemorrhagic fever with renal syndrome (HFRS) caused by Hantann virus or Seoul virus frequently occurs in Korea. The prodromal clinical symptoms are flu-like symptoms. Rapidly progressive renal failure and hemorrhage follow. Hantavirus pulmonary syndrome (HPS) is usually found in the U.S.A., caused by the Sin-nombre virus. The prodromal symptoms resemble HFRS. However, during the third to fith hospital day after admission, pulmonary edema or pulmonary hemorrhage acutely develops, which results in acute respiratory failure. We here report a case of HFRS with HPS that developed in a 47 year-old man. The patient had flu-like symptoms and diarrhea on admission. Acute renal failure developed and acute hemodialysis was performed. On the fourth hospital day, an asymmetric bilateral haziness as seen on a chest X-ray rapidly developed with reduced O2 saturation, and mechanical ventilation was applied. On the eighth hospital day, the patient was weaned from the ventilator. When acute respiratory failure develops in patients with HFRS, HPS might be considered.
Acute Kidney Injury ; Diarrhea ; Hantavirus Pulmonary Syndrome* ; Hantavirus* ; Hemorrhage ; Hemorrhagic Fever with Renal Syndrome* ; Humans ; Korea ; Middle Aged ; Prodromal Symptoms ; Pulmonary Edema ; Renal Dialysis ; Renal Insufficiency ; Respiration, Artificial ; Respiratory Insufficiency ; Seoul virus ; Thorax ; Ventilators, Mechanical

OBJECTIVETo confirm the existence of Amur-like viruses in Apodemus peninsulae in China, and to understand the molecular characteristics of these viruses.

METHODSTotal RNA was extracted from lungs of A. peninsulae captured in Jilin of Northeast China with Trizol reagent. Complete S and partial M segments of Amur virus were amplified and sequenced. Phylogenetic analyses on multiple nucleotide sequences were performed with the Clustal method and DNASTAR software.

RESULTS383 bp cDNA of M segment and 1696 bp of S segment of Amur like virus were recovered from lung tissue of A. peninsulae, named JilinAP06. The full-length of its S gene comprised of 1696 nucleotides with ORF including 1287 nucleotides and encoding a protein which comprised 429 amino acids. The phylogenetic analysis of this sample with other hantaviruses revealed that the complete S and partial M segment sequence of JilinAP06 both were closely related to those Amur viruses such as AP63, AP61, AP1371 and AP1168 found in A. peninsulae from Far East region of Russia and B78 strain, Liu strain and H5 strain, which were all from Chinese patients. The complete S and partial M segment sequence of JilinAP06 had only 81.0% identities with the nucleotide sequences of HV prototype 76-118 strain.

CONCLUSIONAmur-like viruses did exist in A. peninsulae from Northeasern China while A. peninsulae might be the natural reservoir of Amur-like viruses in China and was the important infectious source to HFRS patients which were caused by Amur-like viruses.

Animals ; China ; Hantavirus ; classification ; genetics ; isolation & purification ; Hantavirus Pulmonary Syndrome ; virology ; Humans ; Lung ; virology ; Murinae ; virology ; Open Reading Frames ; genetics ; Phylogeny ; Reverse Transcriptase Polymerase Chain Reaction

Hantaviruses belong to the genus Hantavirus and Hantaan, Seoul, Puumala, Belgrade and Sin Nombre viruses are the etiolgic agents of two serious hantaviral diseases of humans. The rodent hosts and the specific etiologic agents of haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) are known and many reported cases occurred in Eurasia and Americas. Wild rodents trapped in 13 different areas of Korea from 1994 to 1998 were investigated against hantavirus infection. A total of 718 wild rodents and 10 species were trapped and found 630 (87.7%) of them were Apodemus agrarius. Indirect immunofluorescent antibody technique (IFAT) was performed for hantaviruses infections using different hantavirus antigens. Hantavirus antibodies were found in 68 (10.8%) out of 630 A. agrarius, 8 (42.1%) of 19 Rattus norvegicus. Among 68 lungs and other tissues of antibody positive A. agrarius, 5 (7.4%) were antigen positive. IFA titers of 5 positive A. agrarius sera showed higher titers against Puumala or Sin Nombre viruses than Hantaan virus. These results suggest that there may be are possibilities of existence of a noble hantavirus in Korean wild rodents.
Americas ; Animals ; Antibodies ; Fever ; Hantaan virus ; Hantavirus Infections* ; Hantavirus Pulmonary Syndrome ; Hantavirus* ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Korea* ; Lung ; Murinae ; Rats ; Rodentia* ; Seoul ; Sin Nombre virus

Hantavirus infection occuring during pregnancy is rarely progressing to adult respiratory distress syndrome (ARDS), which is accompanied by thrombocytopenia, leukocytosis, fever, oliguria, aggravation of bleeding, hematuria, lactacedemia. Pregnancy may have an unfavorable impact on the pathophysiologic characteristics of ARDS. The high oxygen demands of pregnancy are unable to be matched by oxygen delivery in ARDS and may predispose the patient to multiple organ failure, as well as fetal oxygen deprivation. We present the case with hantavirus pulmonary syndrome complicating pregnancy.
Fever ; Hantavirus Infections ; Hantavirus Pulmonary Syndrome* ; Hantavirus* ; Hematuria ; Hemorrhage ; Humans ; Leukocytosis ; Multiple Organ Failure ; Oliguria ; Oxygen ; Pregnancy* ; Respiratory Distress Syndrome, Adult ; Thrombocytopenia

Hantaviruses, members of the family Bunyaviridae, are causative agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Hantaan (HTN) virus, the etiologic agent of clinically severe HFRS in Far East Asia, Russia and the Balkans, was first isolated in 1976 from lung tissues of striped-field mice (Apodemus agrarius) captured in Songnae-ri, Kyungki-do, Korea. Mitochondrial DNA (mtDNA) in vertebrates evolve very rapidly, and hence it can provide a high resolution for distinguishing between closely related organism and species. To clarify the phylogenetic relationship of HTN viruses with their natural rodent host, a part of M segment of HTN virus and 424-nucleotide region of cytochrome b gene of mtDNA were amplified and sequenced from tissues of striped-field mice by reverse transcription-polymerase chain reaction (RT-PCR) and PCR, respectively. A 324-nucleotide region of G2 glycoprotein-encoding M segment of HTN virus was amplified from lung tissues of A. agrarius mice, revealed 84-86% sequence similarity with Apodemus-borne HTN virus strains from China. The co-speciation of Apodemus-borne hantaviruses with its natural reservoir rodents, A. agrarius and A. flavicollis, be found. A. agrarius rodent population from South Korea had almost same genetic background irrespective of their geographic origin. HTN virus strains from South Korea shared a common ancestry and were evolutionarily distinct from HTN viruses kom China. We have found no evidence for the presence of phylogenetic relationship of A. agrarius-borne Korean HTN virus strains with the genetic diversity of their rodent host captured in Korea based on cytochrome b gene of mtDNA.
Animals ; Asia ; Balkan Peninsula ; Bunyaviridae ; China ; Cytochromes b ; DNA, Mitochondrial* ; Far East ; Genetic Variation ; Gyeonggi-do ; Hantaan virus* ; Hantavirus ; Hantavirus Pulmonary Syndrome ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Korea ; Lung ; Mice* ; Murinae* ; Polymerase Chain Reaction ; Rodentia* ; Russia ; Vertebrates

Hantavirus is a genus of the Bunyaviridae family causing two serious diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Puumala virus is a member of hantavirus originally found in Europe, and its natural reservoir is Clethrionomys glareolus. It is also associated with the hurnan disease nephropathia epidemica, a milder form of HFRS. To identify the hantaviruses in bats, bats were collected from Jeong-Sun, Won-Joo, Chung-Ju and Hwa-Cheon area in Korea, and nested RT-PCR was performed with serotype specific primer from M segment. Interestingly, Puumala virus was detected in bats (Rhinolophus ferrum-equinum) only from Won-Joo. The 327 bp nested RT-PCR product, was sequenced. The sequence database search indicates that the sequence is homologous to the published sequence of Puumala viruses. The sequence similarities were ranged from 71% to 97%. The highest sequence similarity was 97% with Puumala virus Vranicam strain, and the lowest was 71% with Puumala virus K27 isolate. Puumala virus Vranicam strain was isolated from a bank vole (Clethrionomys glareolus) in Bosnia-Hercegovina. Puumala virus K27 was isolated from human in Russia. This analysis confirms that bats (Rhinolophus ferrum-equinum) in Korea are natural reservoir of Puumala virus.
Arvicolinae ; Base Sequence ; Bunyaviridae ; Chiroptera* ; Chungcheongbuk-do ; Europe ; Hantavirus ; Hantavirus Pulmonary Syndrome ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Korea* ; Puumala virus* ; Russia ; Sequence Analysis*

Hantaviruses are members of the family Bunyaviridae, the etiologic agents of Hemorrhagic fever with renal syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS). They are negative-sense, single-stranded RNA viruses possessing a large (L), medium (M) and small (S) genomic segment which encodes a viral polymerase, envelope glycoproteins (G1 and G2) and a nucleocapsid (N) protein, respectively. Seoul (SEO) virus, the causative agent of clinically mild HFRS in worldwide, was isolated from lung tissues of urban rat (Rattus norvegicus) captured in Seoul, Korea, 1982. To clarify the antigenic characteristics and the differentiation of serotypes of hantavirus, 8 hybridoma cell lines secreting monoclonal antibodies (MAbs) against SEOV 80-39 strain were produced by fusion of SP2/0-Ag14 mouse myeloma cells with spleen cells of BALB/c mice, immunized with SEOV. Reactivities of these MAbs were examined by the indirect immunofluorescence assay (IFA), enzyme linked immunosorbent assay (ELISA), immunoblot, high density particle agglutination (HDPA) and plaque reduction neutralization test (PRNT). Eight out of 235 hybridomas secreted MAbs of Seoul virus 80-39 continuously, and these eight MAbs were all IgG. The isotypes of these 8 MAbs are; one clone (F3-3C) was IgG1, six (F1-1B9B, F1-3B, F1-3D, F4-1E, F4-3F, F4- 6C) were IgG2a and one (F1-1B9F) was IgG2b. Seven MAbs (F1-1B9B, F1-1B9F, F1-3B, F1- 3D, F3-3C, F4-1E, F4-3F) reacted with nucleocapsid protein (M.W. 50K) of SEOV by immunoblot. All eight MAbs were cross-reacted with Hantaan (HTN) virus, one (F4-3F) was cross-reacted with Puumala (PUU) virus and two (F1-1B9B, F1-3B) were cross-reacted with Prospect Hill (PH) virus by IFAT. None of these 8 MAbs had neutralizing activity.
Agglutination ; Animals ; Antibodies, Monoclonal* ; Bunyaviridae ; Cell Line ; Clone Cells ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique, Indirect ; Glycoproteins ; Hantavirus ; Hantavirus Pulmonary Syndrome ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Hybridomas ; Immunoglobulin G ; Korea ; Lung ; Mice ; Neutralization Tests ; Nucleocapsid ; Nucleocapsid Proteins ; Rats ; RNA Viruses ; Seoul virus* ; Seoul* ; Spleen

Eleven hantavirus isolates were obtained by innoculation of viremic blood, urine, or autopsy tissue specimens from ten HFRS patients, and sera were obtained from five patients with HFRS. The disease was diagnosed by clinical manifestations and indirect immunofluorescent antibody technique. We obtained 6 hantaviruses from gene bank. So, we analyzed 22 hantavirus samples to elucidate the genetic diversity. The hantaviral RNAs were extracted and 365 base-pair complementary DNAs of M segment were obtained by reverse transcriptase polymerase chain reaction (RT-PCR) and 326 base-pair by nested PCR. The nucleotide sequences of amplified cDNA fragments were determined by the direct sequencing method using automatic DNA sequence analyzer. We got full M segment sequences of 28 reported hantaviruses with medline searching, and aligned them with our 22 samples, and the phylogenetic analysis for nucleotide and amino acid sequences were done by the Clustal method. The nucleotide and amino acid sequences of Hantaan virus 17 samples showed high (above 90%) homology with 76-118 strain, but 2 samples showed significant differences with 76-118 strain and with other 17 samples. The 3 Seoul virus samples showed high intraspecies differences in 1 sample, and showed singnificant differences with SR-11 strain. In phyogenetic tree analysis, Puumala virus and Hantavirus pulmonary syndrome viruses showed high homology, but Hantaan and Seoul viruses showed significant genetic diversity among strains. In conclusion, hantaviruses isolated from HFRS patients showed genetic diversity compared with those isolated from rodent hosts.
Amino Acid Sequence ; Autopsy ; Base Sequence* ; DNA, Complementary ; Genetic Variation ; Hantaan virus ; Hantavirus Pulmonary Syndrome ; Hantavirus* ; Hemorrhagic Fever with Renal Syndrome* ; Humans ; Korea* ; Polymerase Chain Reaction ; Puumala virus ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; Rodentia ; Seoul virus