The first reported hepatitis E outbreak in a food manufacturing factory: Korea, 2022.

OBJECTIVES: On February 16, 2022, 12 cases of hepatitis E virus (HEV) infection were reported in a food manufacturing factory in Korea. The aim of this study was to identify additional cases and to determine the source of this HEV outbreak. METHODS: This study was an in-depth investigation of 12 HEV immunoglobulin M (IgM)-positive cases and their demographic, clinical, and epidemiological characteristics. On-site specimens were collected from the environment and from humans, and a follow-up investigation was conducted 2 to 3 months after the outbreak. RESULTS: Among 80 production workers in the factory, 12 (15.0%) had acute HEV infection, all of whom were asymptomatic. The follow-up investigation showed that 3 cases were HEV IgMpositive, while 6 were HEV IgG-positive. HEV genes were not detected in the HEV IgM-positive specimens. HEV genes were not detected in the food products or environmental specimens collected on-site. HEV was presumed to be the causative pathogen. However, it could not be confirmed that the source of infection was common consumption inside the factory. CONCLUSIONS: This was the first domestic case of an HEV infection outbreak in a food manufacturing factory in Korea. Our results provide information for the future control of outbreaks and for the preparation of measures to prevent domestic outbreaks of HEV infection.

Correction to: Genetic diversity and evolutionary history of Korean isolates of severe fever with thrombocytopenia syndrome virus from 2013-2016.

Authors would like to correct the 4th author name from "Ju-Yeon Lee" to the correct version "Joo-Yeon Lee".

Genetic diversity and evolutionary history of Korean isolates of severe fever with thrombocytopenia syndrome virus from 2013-2016.

Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV). Although SFTS originated in China, it is an emerging infectious disease with prevalence confirmed in Japan, Korea, and Vietnam. The full-length genomes of 51 Korean SFTSV isolates from 2013 to 2016 were sequenced, and the sequences were deposited into a public database (GenBank) and analyzed to elucidate the phylogeny and evolution of the virus. Although most of the Korean SFTSV isolates were closely related to previously reported Japanese isolates, some were closely related to previously reported Chinese isolates. We identified one Korean strain that appears to have resulted from multiple inter-lineage reassortments. Several nucleotide and amino acid variations specific to the Korean isolates were identified. Future studies should focus on how these variations affect virus pathogenicity and evolution.

Genetic and pathogenic diversity of severe fever with thrombocytopenia syndrome virus (SFTSV) in South Korea.

To investigate nationwide severe fever with thrombocytopenia syndrome virus (SFTSV) infection status, we isolated SFTSVs from patients with suspected severe fever with thrombocytopenia syndrome (SFTS) in 207 hospitals throughout South Korea between 2013 and April 2017. A total of 116 SFTSVs were isolated from 3137 SFTS-suspected patients, with an overall 21.6% case fatality rate. Genetic characterization revealed that at least 6 genotypes of SFTSVs were co-circulating in South Korea, with multiple reassortments among them. Of these, the genotype B-2 strains were the most prevalent, followed by the A and F genotypes. Clinical and epidemiologic investigations revealed that genotype B strains were associated with the highest case fatality rate, while genotype A caused only one fatality among 10 patients. Further, ferret infection studies demonstrated varying clinical manifestations and case mortality rates with different strains of SFTSV, which suggests this virus could exhibit genotype-dependent pathogenicity.

Production of Ebola virus-like particles in Drosophila melanogaster Schneider 2 cells.

In this study, we generated recombinant virus-like particles (VLPs) against family Filoviridae, genus Ebolavirus, species Zaire ebolavirus, strain Makona (EBOV) in Drosophila melanogaster Schneider 2 (S2) cells using the EBOV Makona. S2 cells were cotransfected with four viral plasmids encoding EBOV Makona proteins and protein expression was analyzed by immunoblotting. We confirmed that EBOV Makona proteins were successfully expressed in S2 cells. Additionally, we further examined the formation of intracellular and extracellular VLPs by electron microscopy. eVLPs were produced by sucrose gradient ultracentrifugation of S2 cells transfected with EBOV Makona genes, and production of VLPs was confirmed by immunoblot analysis. Collectively, our findings showed that the S2 cell system could be a promising tool for efficient production of eVLPs.

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus Antibodies in Rural Areas, South Korea.

We investigated 1,228 residents of 3 rural areas in South Korea and determined that 50 (4.1%) were positive for severe fever with thrombocytopenia syndrome virus antibodies. Fever and gastrointestinal symptoms in the previous 3 years and career duration were associated with virus seropositivity.

Molecular genomic characterization of tick- and human-derived severe fever with thrombocytopenia syndrome virus isolates from South Korea.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited. METHODOLOGY/PRINCIPAL FINDINGS: In this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV. CONCLUSIONS/SIGNIFICANCE: Full-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia.

Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome During an Outbreak in South Korea, 2013-2015.

Since the first reported case of severe fever with thrombocytopenia syndrome (SFTS) in South Korea in 2013, between 2013 and 2015, we collected 1,697 serum samples from suspected patients who experienced symptoms of SFTS. We performed reverse transcriptase polymerase chain reaction using total RNA extracted from the patients' sera. When viral RNA was detected in the sera, SFTS was diagnosed. Among the 1,697 samples, 170 were positive for SFTS virus. We then analyzed the epidemiologic features of these 170 cases. As a result, we found that the annual number of cases increased steadily. However, the annual case fatality rate exhibited a downward trend. The majority of patients were aged ≥ 60 years, and most cases occurred during May-October in the eastern and southern parts of the country. These results may be useful for effective SFTS control by describing the clinical and epidemiologic features of the disease in South Korea.

Severe Fever with Thrombocytopenia Syndrome Presenting with Hemophagocytic Lymphohistiocytosis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the newly discovered SFTS Bunyavirus, and there have been no case reports of SFTS patients presenting with hemophagocytic lymphohistiocytosis (HLH) in the English literature. We report a case of SFTS presenting with HLH in a 73-year-old immunocompetent male farmer. Although the patient had poor prognostic factors for SFTS, such as old age and central nervous system symptoms, he recovered fully with supportive care.

One-Step Reverse Transcription-Polymerase Chain Reaction for Ebola and Marburg Viruses.

OBJECTIVES: Ebola and Marburg viruses (EBOVs and MARVs, respectively) are causative agents of severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. In 2014, there was a major Ebola outbreak in various countries in West Africa, including Guinea, Liberia, Republic of Sierra Leone, and Nigeria. EBOV and MARV are clinically difficult to diagnose and distinguish from other African epidemic diseases. Therefore, in this study, we aimed to develop a method for rapid identification of the virus to prevent the spread of infection. METHODS: We established a conventional one-step reverse transcription-polymerase chain reaction (RT-PCR) assay for these pathogens based on the Superscript Reverse Transcriptase-Platinum Taq polymerase enzyme mixture. All assays were thoroughly optimized using in vitro-transcribed RNA. RESULTS: We designed seven primer sets of nucleocapsid protein (NP) genes based on sequences from seven filoviruses, including five EBOVs and two MARVs. To evaluate the sensitivity of the RT-PCR assay for each filovirus, 10-fold serial dilutions of synthetic viral RNA transcripts of EBOV or MARV NP genes were used to assess detection limits of viral RNA copies. The potential for these primers to cross react with other filoviruses was also examined. The results showed that the primers were specific for individual genotype detection in the examined filoviruses. CONCLUSION: The assay established in this study may facilitate rapid, reliable laboratory diagnosis in suspected cases of Ebola and Marburg hemorrhagic fevers.

Full-genome sequences of severe Fever with thrombocytopenia syndrome virus, isolated from South Korea in 2014.

Here, we present the full-length genome sequencing of severe fever with thrombocytopenia syndrome (SFTS) virus, isolated from South Korea in 2014. The five Korean strains were compared by phylogenetic analysis with full SFTS genome sequences of two neighboring nations, China and Japan.

Nosocomial transmission of severe fever with thrombocytopenia syndrome in Korea.

Of the 27 healthcare workers (HCWs) who had contact with a fatally ill patient with severe thrombocytopenia syndrome in Korea (SFTS), 4 who were involved in cardiopulmonary resuscitation complained of fever and were diagnosed with SFTS via seroconversion. Exposure to respiratory secretions, blood, or gowns soiled by body fluids was significantly associated with infection of HCWs.

Severe fever with thrombocytopenia syndrome virus, South Korea, 2013.

During 2013, severe fever with thrombocytopenia syndrome was diagnosed in 35 persons in South Korea. Environmental temperature probably affected the monthly and regional distribution of case-patients within the country. Phylogenetic analysis indicated that the isolates from Korea were closely related to isolates from China and Japan.

Prevalence of severe fever with thrombocytopenia syndrome virus in Haemaphysalis longicornis ticks in South Korea.

Haemaphysalis longicornis a vector that harbors severe fever with thrombocytopenia syndrome virus (SFTSV) is a major species of tick in South Korea. To investigate the existence and prevalence of SFTSV in Korea, we collected ticks from nine provinces in South Korea for detecting SFTSV. In all, we collected 13,053 ticks, and H. longicornis (90.8%, 11,856/13,053) was the most abundant among them. The minimum infection rate (MIR) of SFTSV in H. longicornis was 0.46% (55 pools). SFTSV was detected in ticks during all the developmental stages, showing MIR in larvae (2/350, 0.57%), nymphs (38/10,436, 0.36%), males (2/221, 0.90%), and females (13/849, 1.53%), respectively. Viruses were detected in ticks collected between April and September. A higher MIR was detected in ticks from the southern part of the country. We amplified the M and S segment partial genes from a sample and analyzed the nucleotide sequence. The results showed a 93-98% homology to Chinese and Japanese strains registered in Genbank. In this study, we confirmed the existence of SFTSV for the first time in South Korea. The SFTSV prevalence data from the studies are essential for raising the awareness of SFTS in South Korea.

Severe fever with thrombocytopenia syndrome virus in ticks collected from humans, South Korea, 2013.

We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May-October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.

Hantaan virus nucleocapsid protein stimulates MDM2-dependent p53 degradation.

Apoptosis has been shown to be induced and downregulated by the Hantaan virus (HTNV) nucleocapsid (N) protein. To address these conflicting data, expression of the p53 protein, one of the key molecules involved in apoptosis, was assessed in the presence of the N protein in A549 and HeLa cells. The amount of p53, increased by drug treatment, was reduced when cells were infected with HTNV or transfected with an expression vector of the HTNV N protein. When cells were treated with a proteasome inhibitor (MG132) or an MDM2 antagonist (Nutlin-3), p53 expression was not reduced in N protein-overexpressed cells. We concluded that the HTNV N protein ubiquitinates and degrades p53 MDM2-dependently. Here we report downregulation of p53 expression through a post-translational mechanism: MDM2-dependent ubiquitination and degradation by the HTNV N protein. These results indicate that N protein-dependent p53 degradation through the ubiquitin proteasome system is one of the anti-apoptotic mechanisms employed by HTNV.

Silkworm 30K protein inhibits ecdysone-induced apoptosis by blocking the binding of ultraspiracle to ecdysone receptor-B1 in cultured Bm5 cells.

This study investigates the mechanism through which increased 30K protein inhibits ecdysone-induced apoptosis in the Bm5 silkworm ovarian cell line. Treatment of Bm5 cells with 20-hydroxyecdysone (20E) after transfection with the pIZT/V5-His control vector triggered apoptosis, but 20E treatment did not trigger apoptosis in Bm5 cells transfected with the pIZT/30K/V5-His vector. To confirm its inhibitory effect on apoptosis, 30K protein was first purified from Escherichia coli transformed with a 30K expression vector and used to generate specific antibodies in mice. Anti-30K antiserum was used to confirm synthesis of the 30K protein in pIZT/30K/V5-His-transfected Bm5 cells and to detect 30K protein binding to the ecdysone receptor-B1 (EcR-B1). Anti-30K antiserum was used to immunoprecipitate protein complexes containing 30K from Bm5 cells transfected with pIZT/30K/V5-His vector and treated with 20E. We observed that 30K proteins bound primarily to the EcR-B1 and not to ultraspiracle (USP). Reciprocal immunoprecipitation of EcR-B1-containing complexes from Bm5 cells transfected with control pIZT/V5-His vector and treated with 20E showed that EcR-B1 bound to USP in the absence of 30K but did not bind to USP in pIZT/30K/V5-His-transfected Bm5 cells. These results demonstrate that 30K proteins block USP binding to EcR-B1 through formation of a 30K/EcR-B1 complex, resulting in inhibition of 20E-induced Bm5 cell apoptosis.

Increase of 30K protein in identified motoneurons by hemolymph results in inhibition of programmed cell death in silkworm, Bombyx mori (Lepidoptera, Bombycidae).

This study demonstrates that a 30K protein was gradually synthesized in primary-cultured motoneurons from the accessory planta retractor (APR) of the 6th abdominal ganglion (APR6) in silkworm ventral ganglia through stimulation of hemolymph. An increase in 30K protein synthesis resulted in an inhibition of programmed cell death (PCD) of APR6 motoneurons. The 30K protein was gradually synthesized from the 30Kc6 gene of identified APR6s in day-6 4th instars to day-9 5th instar larvae, but synthesis of the 30K protein ceased in isolated APR6s of day-1 pupa, which normally begin to undergo PCD. When pupal APR6s were treated with larval hemolymph, however, the 30K protein was synthesized suggesting the existence of an anti-PCD factor in the larval hemolymph. An increase of 30K protein within the APR6s was confirmed by antiserum made against the recombinant 30K protein that originated from the APR 30Kc6 gene. Larval APR6, in which PCD was induced with 20-hydroxyecdysone (20E) added to the primary culture, exhibited some PCD characteristics of shrinkage of cell bodies, axonal fragmentation and loss of mitochondrial function. These results provide new insights on the survival or PCD of insect motoneurons through stimulation of hemolymph.