Objective: To study the molecular epidemiological characteristics and genotypes of hantavirus carried by rodents in Shenzhen. Methods: Rodents were captured, and their lung samples were collected and grinded for RNA extraction. The hantavirus positive samples were classified by real-time fluorescence PCR. Rat lung nucleic acid samples were selected to amplify the nucleotide sequences of partial M fragments (G2 segment) and S fragments by reverse transcription-nested polymerase chain reaction (RT-nested PCR). The PCR products were then sequenced and homology and phylogenetic tree analyses were conducted. Results: A total of 200 rodents were captured, including 189 Rattus norvegicus, 9 Rattus flavipectus and 2 Mus musculus. The positive rate of hantavirus was 21.0% (42/200), all of the isolates were seoul virus (SEOV) strains. The positive rate of hantavirus in Bao'an district was highest (45.7%), and the difference in detection rate among districts were significant (χ²=25.60,P<0.05). A total of 25 G2 segment sequences and S fragment sequences of SEOV were obtained by virus gene sequencing, and their nucleotide homology was 95.3%-100.0% and 97.6%-100.0%, respectively. Compared with other reference sequences of S2 subtype, the nucleotide homology between the sample sequence and the reference sequence from Guangzhou was high. Analysis on nucleotide homology and phylogenetic tree showed that hantavirus carried by the rodents captured in Shenzhen belonged to SEOV S2 subtype. Analysis on amino acid variation sites revealed that there was a variation in the nucleocapsid protein encoded by S gene from Alanine to Threonine at the 973 position of BA-111. Conclusion: Hantavirus carried by rodents in Shenzhen belongs to S2 subtype of Seoul virus, which have little variation compared with the hantavirus strains obtained in other years in Shenzhen and surrounding provinces.
Mice ; Rats ; Animals ; Orthohantavirus/genetics* ; Rodentia ; Phylogeny ; Hantavirus Infections/veterinary* ; Communicable Diseases ; Nucleotides ; Real-Time Polymerase Chain Reaction

In February 2019, the order Bunyavirales, previously family Bunyaviridae, was amended by new order of 10 families including Hantaviridae family, and now accepted by the International Committee on Taxonomy of Viruses (ICTV). Hantaviridae is now a family of the order Bunyavirales, and the prototype virus species is Hantaan orthohantavirus. The family Hantaviridae is divided into four subfamilies including Mammantavirinae, Repantavirinae, Actantavirinae and Agantavirinae. The subfamily Mammantavirinae is divided into four genera including Orthohantavirus, Loanvirus, Mobatvirus and Thottimvirus. The four Hantavirus species have been found in Korea including three Orthohantaviruses (Hantaan orthohantavirus, Seoul orthohantavirus and Jeju orthohantavirus) and one Thottimvirus (Imjin thottimvirus).
Bunyaviridae ; Classification ; Hantaan virus ; Hantavirus ; Humans ; Korea ; Seoul ; Virology

The Ministry of Food and Drug Safety of Korea made an official announcement in March 2018 that the total number of inoculations of Hantaan virus vaccine (Hantavax®) would change from 3 to 4. Some aspects of this decision remain controversial. Based on the characteristics of Hantaan virus (HTNV) and its role in the pathogenesis of hemorrhagic fever with renal syndrome, it might be difficult to develop an effective and safe HTNV vaccine through the isolate-inactivate-inject paradigm. With the development of high-throughput ‘omics’ technologies in the 21st century, vaccinomics has been introduced. While the goal of vaccinomics is to develop equations to describe and predict the immune response, it could also serve as a tool for developing new vaccine candidates and individualized approaches to vaccinology. Thus, the possibility of applying the innovative field of vaccinomics to develop a more effective and safer HTNV vaccine should be considered.
Hantaan virus ; Hemorrhagic Fever with Renal Syndrome ; Humans ; Immunogenetics ; Korea ; Precision Medicine ; Vaccines ; Vaccines, Synthetic

Objective: To analyze the epidemiological and temporal-spatial distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shandong province during 2010-2016 and provide references for developing prevention and control measures. Methods: Based on the data of Infectious Disease Reporting Information System in China, the incidence and temporal-spatial distribution of HFRS in Shandong from 2010 to 2016 were analyzed by spatial autocorrelation and space-time scan statistics. Results: A total of 9 114 HFRS cases were reported in Shandong during this period. The cases were mainly distributed in age group 30-70 years, and the male to female ratio of the cases was 2.63 ∶ 1. Most cases were farmers. The higher incidence rate was reported in southeastern Shandong, while the lower incidence rate was reported in northwestern Shandong. Among the epidemic periods, the highest incidence rate was 1.87/100 000 in 2013. The results of spatial autocorrelation and space-time scanning indicated that the high-high clusters of HFRS were concentrated in southeastern Shandong and then spread to central Shandong. The cluster mainly occurred from the end of 2011 to the first half of 2015. Both the incidence rate and the cluster decreased in 2016. Conclusions: The epidemic and cluster of HFRS still existed in Shandong from 2010 to 2016. The key areas for the prevention and control of HFRS were in southeastern and central Shandong.
Adolescent ; Adult ; Aged ; China/epidemiology* ; Epidemics ; Female ; Hantaan virus ; Hemorrhagic Fever with Renal Syndrome/virology* ; Humans ; Incidence ; Male ; Seasons ; Spatio-Temporal Analysis ; Young Adult

PURPOSE: We aimed to identify the epidemiology and the clinical characteristics of human parainfluenza virus type 4 (HPIV-4) infection compared to HPIVs 1–3 infections in Korean children. METHODS: We reviewed medical records of children with HPIV infection who visited Seoul National University Children's Hospital from 2015 to 2017. Detection of respiratory viruses was performed using real time-polymerase chain reaction (rt-PCR), which could differentiate HPIVs 1–4. Diagnosis was classified as a febrile illness, upper respiratory tract infection (URI), croup, bronchiolitis, or pneumonia. The epidemiology, demographic features, and clinical characteristics among HPIV types were compared. The clinical data were analyzed only for the previously healthy children. RESULTS: Of the 472 children diagnosed with HPIV infection, 108 (22.9%) were previously healthy: 24 (22.2%), 19 (17.6%), 39 (36.1%), and 26 (24.1%) in HPIV types 1, 2, 3, and 4, respectively. The median age of children with HPIV-4 infection was 11 (0–195) months: the proportion of children aged < 2 years and 2 to < 5 years were 65.4% and 19.2%, respectively. Clinical diagnoses of HPIV-4 infection were bronchiolitis (38.5%), pneumonia (30.8%), and URI (30.8%). Croup was the most prevalent in HPIV-2 (21.1%) and none in HPIV-4 infection (P=0.026). Hospital admission rates among HPIV types were not significantly different (P> 0.05). CONCLUSIONS: We observed seasonal peak of HPIV-4 infection in 2015 and 2017. HPIV-4 was a common respiratory pathogen causing lower respiratory tract infection in hospitalized children.
Bronchiolitis ; Child ; Child, Hospitalized ; Croup ; Diagnosis ; Epidemiology ; Humans ; Medical Records ; Parainfluenza Virus 4, Human ; Paramyxoviridae Infections ; Pneumonia ; Respiratory Tract Infections ; Seasons ; Seoul

We have examined isolation and identification protocols for three virus simulant candidates to biological warfare agents. MS2 phage, a simulant for yellow fever virus and Hantaan virus, was propagated using as a host an E. coli strain with F pilus. MS2 phage genome was examined by reverse transcription and polymerase chain reaction (RT-PCR). Coat protein of the phage preparation was examined by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometric analysis. Cydia pomonella granulosis virus (CpGV) is a virus simulant candidate to smallpox virus. CpGV was isolated from a commercialized CpGV pellet. In this study, we developed new isolation and identification protocols for CpGV. One disadvantage of using CpGV is that it is not easy to determine viability of the virus. Here, we have included T4 phage as an alternative. We established a high titer production protocol and developed an easy genome identification protocol that does not require purified phage DNA. Stability of these virus preparations was also examined under various storage conditions. When the virus preparations were not subjected to freeze drying, MS2 phage was most stable when it was stored in liquid nitrogen but unstable at 4℃. In contrast, T4 phage was most stable when it was stored at 4℃. CpGV was stable at −20℃ but not at 4℃. Stability during or after freeze drying was also investigated. The result showed that 70~80% MS2 survived the freeze drying process. In contrast, only about 15% of T4 phage survived during the freeze drying. CpGV was found to be degraded during freeze drying.
Bacteriophage T4 ; Bacteriophages ; Biological Warfare Agents ; DNA ; Electrophoresis ; Freeze Drying ; Genome ; Granulovirus ; Hantaan virus ; Levivirus ; Nitrogen ; Polymerase Chain Reaction ; Reverse Transcription ; Variola virus ; Yellow fever virus

BACKGROUND: An inactivated Hantaan virus vaccine (iHV) has been broadly used as a preventive strategy for hemorrhagic fever with renal syndrome (HFRS) by the South Korean Army. After the vaccination program was initiated, the overall incidence of HFRS cases was reduced in the military population. While there are about 400 HFRS cases annually, few studies have demonstrated the efficacy of the iHV in field settings. Therefore, this study aimed to evaluate the iHV efficacy on HFRS severity. METHODS: From 2009 to 2017, HFRS cases were collected in South Korean Army hospitals along with patients’ vaccination history. HFRS patients were classified retrospectively into two groups according to vaccination records: no history of iHV vaccination and valid vaccination. Vaccine efficacy on the severity of acute kidney injury (AKI) stage and dialysis events were investigated. RESULTS: The effects of the iHV on renal injury severity in between 18 valid vaccinated and 110 non-vaccinated patients were respectively evaluated. In the valid vaccination group, six of the 18 HFRS patients (33.3%) had stage 3 AKI, compared to 60 of the 110 (54.5%) patients in the non-vaccination group. The iHV efficacy against disease progression (VEp) was 58.1% (95% confidence interval, 31.3% to 88.0%). CONCLUSION: The iHV efficacy against the progression of HFRS failed to demonstrate statistically significant protection. However, different severity profiles were observed between the iHV and non-vaccination groups. Additional studies with larger populations are needed to demonstrate the effectiveness of the iHV in patients with HFRS.
Acute Kidney Injury ; Dialysis ; Disease Progression ; Hantaan virus ; Hantavirus* ; Hemorrhagic Fever with Renal Syndrome* ; Hospitals, Military ; Humans ; Incidence ; Military Personnel ; Preventive Medicine ; Retrospective Studies ; Vaccination

In the 1960-70s, South Korea was still in the position of a science latecomer. Although the scientific research environment in South Korea at that time was insufficient, there was a scientist who achieved outcomes that could be recognized internationally while acting in South Korea. He was Ho Wang Lee(1928~ ) who found Hantann Virus that causes epidemic hemorrhagic fever for the first time in the world. It became a clue to identify causative viruses of hemorrhagic diseases that were scattered here and there throughout the world. In addition, these outcomes put Ho Wang Lee on the global center of research into epidemic hemorrhagic fever. This paper examines how a Korean scientist who was in the periphery of virology could go into the central area of virology. Also this article shows the process through which the virus found by Ho Wang Lee was registered with the international academia and he proceeded with follow-up research based on this progress to reach the level at which he generalized epidemic hemorrhagic fever related studies throughout the world. While he was conducting the studies, experimental methods that he had never experienced encountered him as new difficulties. He tried to solve the new difficulties faced in his changed status through devices of cooperation and connection. Ho Wang Lee's growth as a researcher can be seen as well as a view of a researcher that grew from a regional level to an international level and could advance from the area of non-mainstream into the mainstream. This analytic tool is meaningful in that it can be another method of examining the growth process of scientists in South Korea or developing countries.
Developing Countries ; Follow-Up Studies ; Hantaan virus ; Hemorrhagic Fever with Renal Syndrome* ; Korea* ; Methods ; Virology

BACKGROUND/AIMS: The renal effects of nucleos(t)ide analogs in patients with chronic hepatitis B are controversial. We aimed to compare the impact of entecavir (ETV) and tenofovir (TDF) on renal function in patients with hepatitis B virus (HBV)-related cirrhosis. METHODS: We performed a retrospective cohort study of 235 consecutive treatment-naïve patients with HBV-related cirrhosis who were treated with ETV or TDF between December 2012 and November 2013 at Severance Hospital, Seoul, Korea. RESULTS: Compensated cirrhosis was noted in 183 patients (ETV 130, TDF 53), and decompensated cirrhosis was noted in 52 patients (ETV 32, TDF 20). There were no significant changes in estimated glomerular filtration rates (eGFR) from baseline in either the ETV- or TDF-treated groups at week 96 (Chronic Kidney Disease Epidemiology Collaboration, ETV −1.68% and TDF −5.03%, p=0.358). Using a multivariate analysis, the significant factors associated with a decrease in eGFR >20% were baseline eGFR, diabetes mellitus (DM), and the use of diuretics. The use of antiviral agents and baseline decompensation were not determined to be significant factors. CONCLUSIONS: In patients with HBV-related cirrhosis, TDF has shown similar renal safety to that of ETV over a 2-year period. Renal function should be closely monitored, especially in patients who exhibit decreasing eGFR, DM, and the use of diuretics.
Antiviral Agents ; Cohort Studies ; Cooperative Behavior ; Diabetes Mellitus ; Diuretics ; Epidemiology ; Fibrosis* ; Glomerular Filtration Rate ; Hepatitis B virus ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Humans ; Kidney Diseases ; Korea ; Multivariate Analysis ; Retrospective Studies ; Seoul ; Tenofovir*

PURPOSE: To evaluate the clinical spectrum of posttransplantation lymphoproliferative disorder (PTLD) after solid organ transplantation (SOT) in children. METHODS: We retrospectively reviewed the medical records of 18 patients with PTLD who underwent liver (LT) or kidney transplantation (KT) between January 1995 and December 2014 in Seoul National University Children's Hospital. RESULTS: Eighteen patients (3.9% of pediatric SOTs; LT:KT, 11:7; male to female, 9:9) were diagnosed as having PTLD over the last 2 decades (4.8% for LT and 2.9% for KT). PTLD usually presented with fever or gastrointestinal symptoms in a median period of 7 months after SOT. Eight cases had malignant lesions, and all the patients except one had evidence of Epstein-Barr virus (EBV) involvement, assessed by using in situ hybridization of tumor tissue or EBV viral load quantitation of blood. Remission was achieved in all patients with reduction of immunosuppression and/or rituximab therapy or chemotherapy, although 1 patient had allograft kidney loss and another died from complications of chemotherapy. The first case of PTLD was encountered after the introduction of tacrolimus for pediatric SOT in 2003. The recent increase in PTLD incidence in KT coincided with modification of clinical practice since 2012 to increase the tacrolimus trough level. CONCLUSION: While the outcome was favorable in that all patients achieved complete remission, some patients still had allograft loss or mortality. To prevent PTLD and improve its outcome, monitoring for EBV infection is essential, which would lead to appropriate modification of immunosuppression and enhanced surveillance for PTLD.
Allografts ; Child ; Drug Therapy ; Epstein-Barr Virus Infections ; Female ; Fever ; Herpesvirus 4, Human ; Humans ; Immunosuppression ; In Situ Hybridization ; Incidence ; Kidney ; Kidney Transplantation ; Liver ; Lymphoproliferative Disorders* ; Male ; Medical Records ; Mortality ; Organ Transplantation* ; Retrospective Studies ; Rituximab ; Seoul ; Tacrolimus ; Transplants* ; Viral Load