Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the Banyangvirus genus. SFTS disease has been reported throughout East Asia since 2009 and is characterized by high fever, thrombocytopenia, and leukopenia and has a 12 to 30% case fatality rate. Due to the recent emergence of SFTSV, there has been little time to conduct research into preventative measures aimed at combatting the virus. SFTSV is listed as one of the World Health Organization’s Prioritized Pathogens for research into antiviral therapeutics and vaccine development. Here, we report 2 attenuated recombinant SFTS viruses that induce a humoral immune response in immunized ferrets and confer complete cross-genotype protection to lethal challenge. Animals infected with rHB29NSsP102A or rHB2912aaNSs (both genotype D) had a reduced viral load in both serum and tissues and presented without high fever, thrombocytopenia, or mortality associated with infection. rHB29NSsP102A- or rHB2912aaNSs-immunized animals developed a robust anti-SFTSV immune response against cross-genotype isolates of SFTSV. This immune response was capable of neutralizing live virus in a focus-reduction neutralization test (FRNT) and was 100% protective against a cross-genotype lethal challenge with the CB1/2014 strain of SFTSV (genotype B). Thus, using our midsized, aged ferret infection model, we demonstrate 2 live attenuated vaccine candidates against the emerging pathogen SFTSV

The cap-snatching SFTSV endonuclease domain is an antiviral target

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus with 12%-30% case mortality rates and is related to the Heartland virus (HRTV) identified in the United States. Together, SFTSV and HRTV are emerging segmented, negative-sense RNA viral (sNSV) pathogens with potential global health impact. Here, we characterize the amino-terminal cap-snatching endonuclease domain of SFTSV polymerase (L) and solve a 2.4-Å X-ray crystal structure. While the overall structure is similar to those of other cap-snatching sNSV endonucleases, differences near the C terminus of the SFTSV endonuclease suggest divergence in regulation. Influenza virus endonuclease inhibitors, including the US Food and Drug Administration (FDA) approved Baloxavir (BXA), inhibit the endonuclease activity in in vitro enzymatic assays and in cell-based studies. BXA displays potent activity with a half maximal inhibitory concentration (I

Efficacy and Safety of Incontinence Surgery According to the Surgeon’s Specialty and Performance of a Preoperative Urodynamic Study

Purpose The aim of this study was to analyze the efficacy and to estimate the complication rate of incontinence surgery according to the surgeon’s specialty and whether a preoperative urodynamic study (UDS) was performed, using a nationally representative dataset. Methods We enrolled 356,155 women over 20 years old who had undergone surgery for stress urinary incontinence between 2006 and 2015. Patients were followed for up to 3 years to analyze the reoperation and complication rates. Data were obtained from the National Health Claims Database of the National Health Insurance Service (NHIS) of Korea. Multiple Cox regression analysis was conducted to examine the efficacy and safety of incontinence surgery according to the surgeon’s specialty and whether a preoperative UDS was performed. Results The hazard ratio (HR) for reoperation was significantly higher for procedures performed by nonurologists than for procedures performed by urologists (HR, 1.174; 95% confidence interval [CI], 1.103–1.249). Acute urinary retention, postoperative infections, procedure-associated pain, and other complications were also more common in procedures performed by nonurologists than in those performed by urologists. When stratified by whether a preoperative UDS was performed, the HR for reoperation according to the surgeon’s specialty varied by performance of a preoperative UDS. While the reoperation rate was significantly higher in procedures performed by non-urologists when a preoperative UDS was performed (HR, 1.208; 95% CI, 1.122–1.3), there was no significant difference in the HRs for reoperation according to specialty when a preoperative UDS was not performed. Conclusions This population-based study showed that the postoperative outcomes of incontinence surgery were dependent upon the surgeon’s specialty and that the reoperation rate according to the surgeon’s specialty varied based on whether a preoperative UDS was performed

Severe fever with thrombocytopenia syndrome phlebovirus non-structural protein activates TPL2 signalling pathway for viral immunopathogenesis

Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the World Health Organization Prioritized Pathogens, is an emerging phlebovirus with a high fatality . Owing to the lack of therapies and vaccines , there is a pressing need to understand SFTSV pathogenesis. SFSTV non-structural protein (NSs) has been shown to block type I interferon induction and facilitate disease progression . Here, we report that SFTSV-NSs targets the tumour progression locus 2 (TPL2)-A20-binding inhibitor of NF-κB activation 2 (ABIN2)-p105 complex to induce the expression of interleukin-10 (IL-10) for viral pathogenesis. Using a combination of reverse genetics, a TPL2 kinase inhibitor and Tpl2 mice showed that NSs interacted with ABIN2 and promoted TPL2 complex formation and signalling activity, resulting in the marked upregulation of Il10 expression. Whereas SFTSV infection of wild-type mice led to rapid weight loss and death, Tpl2 mice or Il10 mice survived an infection. Furthermore, SFTSV-NSs P A and SFTSV-NSs K R that lost the ability to induce TPL2 signalling and IL-10 production showed drastically reduced pathogenesis. Remarkably, the exogenous administration of recombinant IL-10 effectively rescued the attenuated pathogenic activity of SFTSV-NSs P A, resulting in a lethal infection. Our study demonstrates that SFTSV-NSs targets the TPL2 signalling pathway to induce immune-suppressive IL-10 cytokine production as a means to dampen the host defence and promote viral pathogenesis

Effects of Marine Microalgae (Schizochytrium sp.) in Prepared Feeds on Growth and Survival Rate of Juvenile Sea Cucumber Apostichopus japoncus

A 60 day feeding experiment was conducted to evaluate the growth performance and survival rate of the sea cucumber Apostichopus japonicus fed on six experimental diets containing different inclusion level of Schizochytrium algae (0%, 2%, 4%, 6%, 8% and 10%) in a recirculating aquaculture system (RAS). After the feeding trial, survival was not significantly different among the dietary treatments. Results showed that diets affected the specific growth rate (SGR), ingestion rate (IR), faeces production rate (FPR) and food conversion efficiency (FCE) of sea cucumber. SGR of sea cucumber fed diet containing 6% Schizochytrium sp algae was significantly higher than that of sea cucumber fed the other diets (P < 0.05). The lowest IR and FPR was found when sea cucumber fed diets containing 10% Schizochytrium sp. Results of the experiment suggest that dietary inclusion with 6% Schizochytrium sp algae may improve growth of juvenile sea cucumber. Such detailed information could be helpful in further development of more appropriate diets for culture of sea cucumber