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Acta Medica Portuguesa Oct 2021Toscana virus (TOSV) is an emerging sandfly-borne virus within the Phlebovirus genus. Although most infections caused by this virus present as asymptomatic or with...
INTRODUCTION
Toscana virus (TOSV) is an emerging sandfly-borne virus within the Phlebovirus genus. Although most infections caused by this virus present as asymptomatic or with minimal symptomatology, TOSV may emerge as a febrile disease or sporadic cases of neurological disease such as meningitis or meningoencephalitis. This pathogen is distributed throughout the Mediterranean basin, along with the spatial distribution of its recognized sandfly vector, Phlebotomus perniciosus. Portugal, after Italy, was the second country considered endemic for this virus, with the first case of acquired infection published in 1985. Although little is known about the circulation of this virus in Portugal, the laboratory diagnosis of TOSV is available at the Centre for Vectors and Infectious Diseases Research of the National Institute of Health Dr. Ricardo Jorge (CEVDI/INSA), since 2007. The aim of this study is to report the results of the diagnosis of TOSV at the CEVDI/INSA, between 2009 and 2018.
MATERIAL AND METHODS
The diagnosis of TOSV in the CEVDI/INSA is included in the arboviruses and vector-borne neurotropic viruses panels or can be performed, when specified, for TOSV only. Direct detection is made in cerebrospinal fluid samples and is available for TOSV by specific real-time reverse transcription polymerase chain reaction followed by conventional real-time reverse transcription polymerase chain reaction for sequencing purposes, if positive. For indirect diagnosis, performed in serum samples, an in-house immunofluorescence assay for the detection of IgM and IgG antibodies against TOSV is used. A commercial immunofluorescence assay consisting in a mosaic of four phleboviruses is also available, in which, in addition to TOSV, antibody detection for sandfly fever Naples virus, sandfly fever Sicilian virus and sandfly fever Cyprus virus can be done. All diagnostic tests requested by clinicians to the CEVDI/INSA for arboviruses, neurotropic viruses and/or TOSV between January 2009 and December 2018, were included in this study.
RESULTS
During the study period, the CEVDI/INSA received samples from 608 patients with diagnostic requests for TOSV. Five acute TOSV infections and one acute sandfly fever Sicilian virus infection were confirmed in serum samples. Three other patients had serological evidence of previous contact with the virus. Two of the six patients with acute infection developed febrile syndrome, and the other four presented with neurological disease: meningitis (n = 2), meningoencephalitis (n = 1) and severe depression of consciousness (n = 1). These infections were most likely acquired in the districts of Faro (3), Lisbon (2) and Setúbal (1).
DISCUSSION
In Portugal, the number of laboratory diagnostic requests for TOSV is low when compared to the numbers of requests for other less prevalent vector-borne viruses. The Faro district presented the highest number of TOSV-specific diagnostic requests which seems to indicate a higher level of recognition by clinicians in that region. Febrile syndrome and neurological disease were the clinical manifestations that were present in acute cases. In this study, in addition to the Faro district, recent infections were also detected in the districts of Lisbon and Setúbal. It is probable that TOSV may be distributed throughout the mainland territory since its main vector is present from north to south. In 2017, the sandfly fever Sicilian virus was associated for the first time with human disease in our country, thus alerting to the circulation of this phlebovirus.
CONCLUSION
Even though the number of identified cases in Portugal is low, TOSV circulates and causes disease in our country. The diagnosis of this and other phleboviruses should not be neglected in the differential diagnosis of febrile syndrome and viral meningitis and meningoencephalitis, especially during the warmer months, when the vector's activity is higher.
Topics: Antibodies, Viral; Diagnosis, Differential; Humans; Immunoglobulin G; Portugal; Sandfly fever Naples virus
PubMed: 34051876
DOI: 10.20344/amp.13308 -
Virology Apr 2021The heartland virus (HRTV) is a novel phlebovirus that causes severe infections in the USA and closely related to the severe fever thrombocytopenia syndrome virus...
The heartland virus (HRTV) is a novel phlebovirus that causes severe infections in the USA and closely related to the severe fever thrombocytopenia syndrome virus (SFTSV), a causative agent for SFTS in Asia. The entry mechanisms of HRTV remain unclear. Here, we developed the pseudotyped vesicular stomatitis virus bearing the HRTV glycoprotein (GP) (HRTVpv), and the antigenicity and the entry mechanisms of HRTV were analyzed. HRTVpv was neutralized by anti-SFTSV Gc antibody, but not the anti-SFTSV Gn antibodies. Entry of HRTVpv to cells was inhibited by bafilomycin A1 and dynasore, and but it was enhanced in cells overexpressed with C-type lectins. Production of infectious HRTVpv and SFTSVpv was reduced by Nn-DNJ, α-glucosidase inhibitor. The entry of HRTV occurs via pH- and dynamin-dependent endocytosis. Furthermore, Nn-DNJ may be a possible therapeutic agent against HRTV and SFTSV.
Topics: 1-Deoxynojirimycin; Animals; Bunyaviridae Infections; Cell Line; Cricetinae; Haplorhini; Humans; Mice; Phlebovirus; Vesicular Stomatitis; Vesiculovirus; Viral Envelope Proteins; Virus Internalization
PubMed: 33561699
DOI: 10.1016/j.virol.2020.10.006 -
Science Advances May 2022Endogenous viral elements (EVEs), accounting for 15% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode EVEs are particularly diverse...
Endogenous viral elements (EVEs), accounting for 15% of our genome, serve as a genetic reservoir from which new genes can emerge. Nematode EVEs are particularly diverse and informative of virus evolution. We identify Atlas virus-an intact retrovirus-like EVE in the human hookworm , with an envelope protein genetically related to G-G glycoproteins from the family Phenuiviridae. A cryo-EM structure of Atlas G reveals a class II viral membrane fusion protein fold not previously seen in retroviruses. Atlas G has the structural hallmarks of an active fusogen. Atlas G trimers insert into membranes with endosomal lipid compositions and low pH. When expressed on the plasma membrane, Atlas G has cell-cell fusion activity. With its preserved biological activities, Atlas G has the potential to acquire a cellular function. Our work reveals structural plasticity in reverse-transcribing RNA viruses.
Topics: Ancylostomatoidea; Animals; Humans; Phlebovirus; RNA Viruses; Viral Envelope Proteins; Viral Fusion Proteins; Virus Internalization
PubMed: 35544562
DOI: 10.1126/sciadv.abj6894 -
Journal of Medical Virology Jul 2022Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (SFTSV) is a serious public health concern in endemic areas, particularly in Asian and...
Severe fever with thrombocytopenia syndrome (SFTS) caused by Dabie bandavirus (SFTSV) is a serious public health concern in endemic areas, particularly in Asian and Southeast Asian countries. SFTSV is transmitted by direct contact with body fluids from infected humans and animals. Therefore, environmental hygiene in hospitals and veterinary clinics in SFTSV-endemic areas is highly important. This study assessed the effects of continuous and intermittent irradiation with deep-ultraviolet light-emitting diode (DUV-LED) on SFTSV. Evaluation was performed by conducting plaque assay in which SFTSV irradiated with deep-ultraviolet (DUV; 280 ± 5 nm) was inoculated onto Vero cells. The results showed that continuous and intermittent irradiation for 5 s, resulting in 18.75 mJ/cm of cumulative UV exposure, led to a >2.7 and >2.9 log reduction, respectively, corresponding to a >99.8% reduction in infectivity. These results demonstrate that DUV can be utilized for inactivation of SFTSV to maintain environmental hygiene in hospitals and veterinary clinics in endemic countries.
Topics: Animals; Bunyaviridae Infections; Chlorocebus aethiops; Humans; Phlebovirus; RNA Viruses; Severe Fever with Thrombocytopenia Syndrome; Ultraviolet Rays; Vero Cells
PubMed: 35246855
DOI: 10.1002/jmv.27698 -
PLoS Neglected Tropical Diseases Aug 2021With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe...
With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in 2013, the number of reported cases has increased annually in South Korea. However, although tick-borne encephalitis virus (TBEV) was detected from ticks and wild rodents, there is no human TBE case report in South Korea. This study aimed to determine the seroprevalence of TBEV and SFTS virus (SFTSV) among forest and field workers in South Korea. From January 2017 to August 2018, a total 583 sera were obtained from the forest and field workers in South Korea. IgG enzyme-linked immunosorbent assay (ELISA) and neutralization assay were conducted for TBEV, and indirect immunofluorescence assay (IFA) and neutralization assay were performed for SFTSV. Seroprevalence of TBEV was 0.9% (5/583) by IgG ELISA, and 0.3% (2/583) by neutralization assay. Neutralizing antibody against TBEV was detected in a forest worker in Jeju (1:113) and Hongcheon (1:10). Only 1 (0.2%) forest worker in Yeongju was seropositive for SFTSV by IFA (1:2,048) and neutralizing antibody was detected also. In conclusion, this study shows that it is necessary to raise the awareness of physicians about TBEV infection and to make efforts to survey and diagnose vector-borne diseases in South Korea.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Neutralizing; Antibodies, Viral; Encephalitis Viruses, Tick-Borne; Encephalitis, Tick-Borne; Female; Forestry; Humans; Male; Middle Aged; Phlebovirus; Republic of Korea; Seroepidemiologic Studies; Severe Fever with Thrombocytopenia Syndrome; Vector Borne Diseases; Young Adult
PubMed: 34407077
DOI: 10.1371/journal.pntd.0009687 -
Viruses May 2021Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating... (Review)
Review
Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been described as a potent interferon antagonist and NF-κB agonist, two divergent signaling pathways in many immune responses upon a viral encounter. In this review, we highlight the many mechanisms used by NSs on the host that promote viral replication and hyper-inflammation. Understanding these host-pathogen interactions is crucial for antiviral therapy development.
Topics: Animals; Biomarkers; Cytokine Release Syndrome; Cytokines; Disease Models, Animal; Disease Susceptibility; Host-Pathogen Interactions; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Viral Nonstructural Proteins; Virus Replication
PubMed: 34064604
DOI: 10.3390/v13050876 -
Antiviral Research Jan 2021Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host...
Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host inflammatory response, which contributes to pathogenesis. Here, we established two separate minigenome (MG) systems based on the M-segment of SFTSV and HRTV. Following characterization of both systems for SFTSV and HRTV, we used them as a platform to screen potential compounds that inhibit viral RNA synthesis. We demonstrated that the NF-κB inhibitor, SC75741, reduces viral RNA synthesis of SFTSV and HRTV using our MG platform and validated these results using infectious SFTSV and HRTV. These results may lead to the use of MG systems as potential screening systems for the identification of antiviral compounds and yield novel insights into host-factors that could play role in bandavirus transcription and replication.
Topics: Animals; Antiviral Agents; Chlorocebus aethiops; Drug Discovery; Genome, Viral; HEK293 Cells; Host-Pathogen Interactions; Humans; Inhibitory Concentration 50; NF-kappa B; Phlebovirus; THP-1 Cells; Ticks; Vero Cells
PubMed: 33296695
DOI: 10.1016/j.antiviral.2020.104993 -
Frontiers in Immunology 2021Aspergillus-related disease was confirmed to be associated with immune disorders in patients, severe patients with severe fever with thrombocytopenia syndrome (SFTS)...
Aspergillus-related disease was confirmed to be associated with immune disorders in patients, severe patients with severe fever with thrombocytopenia syndrome (SFTS) infected by novel phlebovirus were confirmed to have severe immune damage including cellular immunosuppression and cytokine storms. Secondary invasive pulmonary aspergillosis (IPA) in severe SFTS patients can increase fatality rate. This study investigated early-warning predictive factors of secondary IPA in severe SFTS patients. Receiver operating characteristic analysis was used to assess the value of immune parameters to predict IPA in SFTS patients. The cut-off values of CD4 and CD8 T-cell counts to predict IPA were 68 and 111 cells/mm, with sensitivities of 82.6% and 72%, and specificities of 56.7% and 83.3%, respectively. Cut-off values of IL-6, TNF-α, IL-8, and IL-10 to predict IPA incidence in critically ill SFTS patients were 99 pg/mL, 63 pg/mL, 120 pg/mL, and 111 pg/mL, with sensitivities of 90.0%, 86.7%, 83.3% and 90.0% and specificities of 80.4%, 71.7%, 82.6% and 65.2%, respectively. Lower CD4 and CD8 T-cells counts, higher levels of IL-6, TNF-α, IL-8 and IL-10, higher incidence of pancreatic and renal damage, early antibacterial therapy of carbapenems, and intensive care unit admission were risk factors of IPA in SFTS patients. Multivariate logistic regression analysis indicated counts of CD4 T-cells <68 cells/mm combined with CD8 T-cells <111 cells/mm (odds ratio [OR] 0.218, 95% confidence interval [CI] 0.059-0.803, =0.022), IL-6 >99 pg/ml combined with IL-10 >111 pg/ml (OR 17.614, 95% CI 2.319-133.769, =0.006), and brain natriuretic peptide level >500 pg/ml (OR 13.681, 95% CI 1.994-93.871, =0.008) were independent risk factors for IPA in SFTS patients. The mortality in the IPA group was significantly higher than in the non-IPA group (=0.001). Early antifungal treatment of IPA patients was significantly associated with improved survival (log-rank, =0.022). Early diagnosis of IPA and antifungal treatment can improve the prognosis of SFTS patients. Besides, we speculate SFTS may be as a host factor for IPA.
Topics: Aged; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Early Diagnosis; Female; Humans; Invasive Pulmonary Aspergillosis; Lymphocyte Count; Male; Middle Aged; Phlebotomus Fever; Phlebovirus; Prognosis; ROC Curve; Risk Factors; Severe Fever with Thrombocytopenia Syndrome; Severity of Illness Index; Survival Analysis
PubMed: 34025635
DOI: 10.3389/fimmu.2021.576640 -
Viruses Nov 2023Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans....
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans. In recent years, cases of contact infection with SFTSV via bodily fluids of infected dogs and cats have been reported. In this study, clinical and virological analyses were performed in two dogs in which SFTSV infection was confirmed for the first time in the Toyama prefecture. Both dogs recovered; however, one was severely ill and the other mildly ill. The amount of the SFTSV gene was reduced to almost similar levels in both dogs. In the dogs' sera, the SFTSV gene was detected at a low level but fell below the detection limit approximately 2 weeks after onset. Notably, the SFTSV gene was detected at levels several thousand times higher in urine than in other specimens from both dogs. Furthermore, the gene was detected in the urine for a long period of >2 months. The clinical signs disappeared on days 1 or 6 after onset, but infectious SFTSV was detected in the urine up to 3 weeks later. Therefore, it is necessary to be careful about contact with bodily fluids, especially urine, even after symptoms have disappeared.
Topics: Humans; Animals; Dogs; Cats; Severe Fever with Thrombocytopenia Syndrome; Cat Diseases; Bunyaviridae Infections; Dog Diseases; Phlebovirus
PubMed: 38005905
DOI: 10.3390/v15112228 -
Emerging Infectious Diseases Apr 2020We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%)...
We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.
Topics: Animals; Body Fluids; Bunyaviridae Infections; Cats; Dogs; Humans; Japan; Phlebotomus Fever; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Tick Bites
PubMed: 32186502
DOI: 10.3201/eid2604.191011