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The etiological agent of severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus that was first identified in China in 2009. We have developed and validated a one-step, single-tube, reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of SFTS bunyavirus (SFTSV). This assay demonstrated high specificity and sensitivity, with a detection limit of 10 TCID ml. When combined with the fluorescent detection reagent (FDR) method, results could be determined by observing a color change within 30 min. As an accurate, rapid, simple and low-cost diagnostic method, this RT-LAMP assay will be helpful for detecting and preventing further SFTSV infection in China. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection. Ren et al. generate a panel of monoclonal antibodies (mAbs) that recognize distinct epitopes on the glycoprotein Gn and neutralize severe fever with thrombocytopenia syndrome virus (SFTSV) by diverse mechanisms. One most potent mAb targeting the Gn domain I provides protection against lethal SFTSV infection in mice. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a severe systemic inflammatory response syndrome caused by a potentially lethal tick-borne SFTS virus. A rapid and robust extrafollicular B-cell response to fatal or sublethal SFTS virus infection is known to generate a robust extrafollicular B-cell response that is skewed to lambda-monotypic B-blasts. We present a case of fatal SFTS virus infection-associated histiocytic necrotizing lymphadenitis showing an effaced nodal architecture due to florid lambda-monotypic B-blasts that can raise a diagnostic pitfall in hematopathology. We examined histologic and immunophenotypic features of inguinal lymph node tissue of a 49-year-old Korean woman, who presented with a high fever and painful left inguinal lymphadenopathy associated with fatal SFTS virus infection. The nodal architecture of the excised lymph node appeared to be diffusely effaced by expanded paracortical zones by an extensive proliferation of immunoblast-like large lymphoid cells along with minor foci of necrosis associated with infiltration of phagocytosing histiocytes, featuring the proliferative phase of Kikuchi-Fujimoto disease. Immunophenotypically, however, the proliferating cells consisted predominantly of lambda-monotypic B-blasts. This misleading aberrant B-cell response should be recognized by pathologists to avoid misinterpretation of the lambda-monotypic B-blast proliferation in SFTS viral infection-associated histiocytic necrotizing lymphadenitis as diffuse large B-cell lymphoma. [ABSTRACT FROM AUTHOR]

We designed a highly sensitive reverse transcription nested polymerase chain reaction targeting the M-segment (NPCR-M) of severe fever with thrombocytopenia syndrome (SFTS) virus. NPCR-M was performed in parallel with three other referenced PCR assays QPCR-S, PCR-M, and NPCR-S to assess their clinical usefulness as routine diagnostic techniques for SFTS. In this multi-centered prospective study, 122 blood samples from 38 laboratory-confirmed SFTS patients and 85 control samples were used. The results demonstrated that QPCR-S and NPCR-S had better sensitivity rate up to 21 days after symptom onset however, the PCR-M showed poor sensitivity after 7 days of symptom onset. Our designed NPCR-M had a higher detection rate up to 40 days from symptom onset and revealed the persistence of SFTSV RNA in the early convalescent phase. No false-positive results were seen for the control samples. Additionally, NPCR-M showed positive results for a sample that initially showed negative results from other PCRs and for many other samples collected in the convalescent phase of SFTS. Our designed nested PCR is suitable for SFTSV detection in patients' blood collected in the acute and early convalescent phase of SFTS, and shows better sensitivity and high specificity even up to 40 days after symptom onset. [ABSTRACT FROM AUTHOR]

Ticks can transmit numerous pathogens and harbor diverse microbial communities. Considerable progress has been made in the characterization of the bacterial profiles of ticks, whereas other members of tick microbiota (such as fungi and viruses) and the functional characteristics of ticks warrant further exploration. To investigate the taxonomic and functional profiles and explore potential pathogens they were carrying, samples of different developmental stages and of both sexes of Haemaphysalis longicornis were collected in the present study and the metagenomic deep sequencing method was applied. Metagenomic deep sequencing results revealed that bacteria were predominant, followed by fungi, viruses, archaea and metazoans. Proteobacteria was the dominant phylum in the microbiota of H. longicornis. The abundance of microbial species varied significantly among groups, the bacteria of nymphs and female adults demonstrated unique characteristics, and the microbial community of males overlapped with those of nymphs and females. Functional annotation results demonstrated that the metagenomic sequences of the three groups were classified under metabolism, genetic information processing, environmental information processing and cellular processes. Differences in functional characteristics were observed in both the pathways composition and abundance of carbohydrate-active enzymes. Furthermore, whole metagenome sequencing helped to elucidate the diversity of pathogens carried by H. longicornis, which may facilitate further research attempting to prevent and control tick-borne diseases. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emergent tick-borne bunyavirus first discovered in 2009 in China. SFTSV is a growing public health problem that may become more prominent owing to multiple competent tick-vectors and the expansion of human populations in areas where the vectors are found. Although tick-vectors of SFTSV are found in a wide geographic area, SFTS cases have only been reported from China, South Korea, Vietnam, and Japan. Patients with SFTS often present with high fever, leukopenia, and thrombocytopenia, and in some cases, symptoms can progress to severe outcomes, including hemorrhagic disease. Reported SFTSV case fatality rates range from ~5 to >30% depending on the region surveyed, with more severe disease reported in older individuals. Currently, treatment options for this viral infection remain mostly supportive as there are no licensed vaccines available and research is in the discovery stage. Animal models for SFTSV appear to recapitulate many facets of human disease, although none of the models mirror all clinical manifestations. There are insufficient data available on basic immunologic responses, the immune correlate(s) of protection, and the determinants of severe disease by SFTSV and related viruses. Many aspects of SFTSV virology and epidemiology are not fully understood, including a detailed understanding of the annual numbers of cases and the vertebrate host of the virus, so additional research on this disease is essential towards the development of vaccines and therapeutics. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is being reported annually in South Korea since its first detection there in 2010. The causal agent is a negative-strand RNA virus 80–100 nm in diameter. It causes fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and neural symptoms. The mortality rate of SFTS was 32.6% among 172 cases reported from 2012 to 2015 in South Korea. Thus, is necessary to develop an effective diagnostic method that selectively identifies the isolates circulating in South Korea. The real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay is a simple, rapid, and sensitive approach for molecular diagnosis. Here, we designed novel primers for this assay and found that the technique had very high specificity, sensitivity, and efficiency. This real-time RT-LAMP approach using the novel primers developed herein can be applied for early diagnosis of SFTSV strains in South Korea to reduce the mortality rate of SFTS. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV). Hubei Province is a major epidemic area for SFTS in China. In this study, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and serological testing (IgM) were used simultaneously for laboratory detection of SFTS; however, testing results showed poor consistency between these two methods. Further analysis revealed that time post-onset was the main factor leading to inconsistent results. Thus, qRT-PCR is unable to detect all SFTS cases, and serological testing is essential. Here, 15 strains of SFTSV were successfully isolated from serum samples of acute SFTSV infection and their complete genomes were sequenced and submitted to GenBank. Phylogenetic analysis showed that the 15 SFTS virus strains clustered into four independent genotypes (A, B, D, and E), demonstrating that at least four genotypes of SFTSV have been co-circulating in Hubei Province. Furthermore, four strains of our isolates (HB2014-31, HB2014-35, HB2014-36, and HB2014-37) clustered in genotype E, which was the predominant genotype in Japan and South Korea. In this study, we identified multiple co-prevalent genotypes and confirmed the existence of genotype E viruses circulating in the Dabie Mountains of Hubei, central China. We concluded that SFTSV strains from Hubei exhibit most of the genetic diversity found in China. [ABSTRACT FROM AUTHOR]

The aim of this study was to detect severe fever with thrombocytopenia syndrome virus (SFTSV) infection using polymerase chain reaction (PCR) amplification in adult Haemaphysalis concinna ticks. A total of 72 adult H. concinna ticks were obtained from 35 goats, three adult H. concinna ticks (4.17 %) collected from two goats were found to be infected with SFTSV via PCR assay. Sequence analysis showed that the partial segment M glycoprotein gene of SFTSV was about 500 bases long by polymerase chain reaction (PCR) amplification and that the PCR products from the samples had an identical sequence (KP714259). With regard to the phylogenetic analysis, the Nei-Gojobri (Kimura 2-parameter) method was used to construct the phylogenetic trees. Phylogenetic analysis indicated that the obtained sequence closely resembled SFTSV strain from Zhejiang Province (KC189856) and belonged to the same clade. The similarity of these strains was up to 96.62 % (only differing by 17 bases). In addition, phylogenetic analysis also indicated that the sequence obtained from adult H. concinna ticks was most closely related to the sequence isolated from Haemaphysalis longicornis (KF781498) with 97.22 % similarity (differing only by 4 bases) and belonged to the same clade. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS virus (SFTSV) with a high fatality rate. But the immunofunction was still unclear. The objective of our study was to assess the immunofunction in SFTS patients. Immunofunction test with flow cytometry which contains CD3+, CD4+ and CD8+ T lymphocytes, B cells and NK cells would be used for detecting serum samples collected from 34 SFTS cases and 20 healthy donors. We found that CD3+ and CD4+ T lymphocytes were significantly diminished in SFTS compared to normal control. In contrast, the percentage of NK cells was elevated. Further analysis revealed that the number of CD3+ and CD4+ T lymphocytes showed that there was a more robust pattern of depression in acute phase and severe SFTS infection compared to the patients in recovery phase and mild SFTS infection. But NK cells were significantly increased in acute phase and severe SFTS. They reverted to the near normal levels in convalescent phase. Additionally, the levels of CD3+ and CD4+ T lymphocytes progressively decreased in death group when compared with the survival group, but the level of B cells was higher. The damages of immune system were obvious, and the immune dysfunction might be partly responsible for disease progression of patients with SFTSV infection. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and evaluate a two-tube multiplex real-time RT-PCR assay for the detection and identification of four viral hemorrhagic fever (VHF) pathogens, severe fever with thrombocytopenia syndrome virus (SFTSV), Hantaan virus (HTNV), Seoul virus (SEOV), and dengue virus (DENV), from human clinical samples. The two-tube multiplex real-time RT-PCR assay we developed has a sensitivity of 10 copies/μL for each of the targets, and the performance was linear within the range of at least 10 transcript copies. Moreover, we evaluated the specificity of the assay using other virus RNA as template, and found no cross-reactivity. This new assay is able to detect SFTSV, HTNV, SEOV and DENV in two reactions and brings a cost of 40 % compared to separate reactions. Evaluation of this assay with clinical serum samples from laboratory-confirmed patients and healthy donors showed 100 % clinical diagnostic sensitivity and over 99 % specificity. The assay was applied for scanning 346 clinical samples collected from patients admitted to the hospital with suspected VHF and compared with virus isolation and immunofluorescence assay (IFA). The assay indentified 59 SFTSV-, 12 HTNV-, 11 SEOV- and 9 DENV-positive samples and showed higher sensitivity. This assay thus provides a reliable and cost-effective screening tool for early clinical diagnosis of SFTSV, HTNV, SEOV and DENV in the acute phase. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in rural areas of China and is caused by a new bunyavirus, SFTSV, named after the disease. The transmission vectors and animal hosts of SFTSV are unclear. Ticks are the most likely transmission vectors and domestic animals, including goats, dogs, and cattle, are potential amplifying hosts of SFTSV. The clinical symptoms of SFTS are nonspecific, but major symptoms include fever, gastrointestinal symptoms, myalgia, dizziness, joint pain, chills, and regional lymphadenopathy. The most common abnormalities in laboratory test results are thrombocytopenia (95%), leukocytopenia (86%), and elevated levels of serum alanine aminotransferase, aspartate aminotransferase, creatine kinase, and lactate dehydrogenase. The fatality rate for SFTS is 12% on average, and the annual incidence of the disease is approximately five per 100000 of the rural population. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia virus (SFTSV) is an emerging tick-borne phlebovirus that causes lethal human disease, for which there are no licensed antiviral vaccines or therapies. Herein, we developed a live attenuated recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate expressing the SFTSV Gn/Gc glycoproteins (rVSV-SFTSV/AH12-GP). High titers of cross-protective, broadly neutralizing antibodies were elicited by a single dose of rVSV-SFTSV/AH12-GP in both immunocompetent and immunocompromised mice against multiple strains of SFTSV and the related but distinct phlebovirus Heartland virus (HRTV). Remarkably, complete protection against lethal challenge with SFTSV was conferred in young and old immunocompromised mice irrespective of any pre-existing vector-specific immunity. Collectively, these results suggest that a rVSV vector expressing SFTSV glycoproteins is a promising candidate vaccine against two emerging phleboviruses associated with severe human diseases. Emerging viruses: SFTSV vaccine Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) is an emerging East-Asian arbovirus with a high case fatality that lacks an effective vaccine. Aihua Zheng and colleagues at the Chinese Academy of Sciences generate a recombinant vesicular stomatitis-based vaccine vector expressing SFTSV glycoproteins that are the main targets of neutralizing antibodies. This attenuated rVSV-SFTSV vaccine elicits potent neutralizing antibodies in both young and aged mice but also in severely immunocompromised mice deficient in the type I interferon receptor (Ifnar–/–). Pre-existing vector-specific immunity did not compromise the generation of neutralizing antibodies. Importantly, rVSV-SFTSV could completely and durably protect Ifnar–/– mice from lethal challenge with SFTSV. Serum transfer from immunized mice demonstrates protection is in large part mediated by antibodies. rVSV-SFTSV based approaches might therefore represent a promising vaccine candidate for a potentially important emerging virus. [ABSTRACT FROM AUTHOR]

Infection in humans by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus transmitted by ticks, is often associated with pronounced liver damage, especially in fatal cases. Little has been known, however, about how liver cells respond to SFTSV and how the response is regulated. In this study we report that proinflammatory cytokines were induced in liver tissues of C57/BL6 mice infected with SFTSV, which may cause tissue necrosis in mice. Human liver epithelial cells were susceptible to SFTSV and antiviral interferon (IFN) and IFN-inducible proteins were induced upon infection. We observed that infection of liver epithelial cells led to significant increases in proinflammatory cytokines and chemokines, including IL-6, RANTES, IP-10, and MIP-3a, which were regulated by NFκB signaling, and the activation of NFκB signaling during infection promoted viral replication in liver epithelial cells. Viral nonstructural protein NSs was inhibitory to the induction of IFN-β, but interestingly, NFκB activation was enhanced in the presence of NSs. Therefore, NSs plays dual roles in the suppression of antiviral IFN-β induction as well as the promotion of proinflammatory responses. Our findings provide the first evidence for elucidating host responses and regulation in liver epithelial cells infected by an emerging bunyavirus. [ABSTRACT FROM AUTHOR]

The article offers news briefs related to public health. The Great Britain Health Protection Agency reveals that the number of persons diagnosed with HIV in the country have almost doubled from 1,950 in 2001 to 3,780 in 2010. A study also reveals that half of men might have human papillomavirus (HPV) infection which is a sexually communicable disease that can lead to cancer. Furthermore, over 21,000 individuals were reported having whooping cough in the U.S. in 2010, the highest since 2005.