Pathogenesis and virulence of Heartland virus.

Heartland virus (HRTV), an emerging tick-borne pathogenic bunyavirus, has been a concern since 2012, with an increasing incidence, expanding geographical distribution, and high pathogenicity in the United States. Infection from HRTV results in fever, thrombocytopenia, and leucopenia in humans, and in some cases, symptoms can progress to severe outcomes, including haemorrhagic disease, multi-organ failure, and even death. Currently, no vaccines or antiviral drugs are available for treatment of the HRTV disease. Moreover, little is known about HRTV-host interactions, viral replication mechanisms, pathogenesis and virulence, further hampering the development of vaccines and antiviral interventions. Here, we aimed to provide a brief review of HRTV epidemiology, molecular biology, pathogenesis and virulence on the basis of published article data to better understand this virus and provide clues for further study.

Inhibitory interactions of the 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one scaffold with Bunyavirales cap-snatching endonucleases expose relevant drug design features.

The World Health Organization (WHO) identifies several bunyaviruses as significant threats to global public health security. Developing effective therapies against these viruses is crucial to combat future outbreaks and mitigate their impact on patient outcomes. Here, we report the synthesis of some isoindol-1-one derivatives and explore their inhibitory properties over an indispensable metal-dependent cap-snatching endonuclease (Cap-ENDO) shared among evolutionary divergent bunyaviruses. The compounds suppressed RNA hydrolysis by Cap-ENDOs, with IC50 values predominantly in the lower µM range. Molecular docking studies revealed the interactions with metal ions to be essential for the 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one scaffold activity. Calorimetric analysis uncovered Mn2+ ions to have the highest affinity for sites within the targets, irrespective of aminoacidic variations influencing metal cofactor preferences. Interestingly, spectrophotometric findings unveiled sole dinuclear species formation between the scaffold and Mn2+. Moreover, the complexation of two Mn2+ ions within the viral enzymes appears to be favourable, as indicated by the binding of compound 11 to TOSV Cap-ENDO (Kd = 28 ± 3 µM). Additionally, the tendency of compound 11 to stabilize His+ more than His- Cap-ENDOs suggests exploitable differences in their catalytic pockets relevant to improving specificity. Collectively, our results underscore the isoindolinone scaffold's potential as a strategic starting point for the design of pan-antibunyavirus drugs.

Modeling Heartland virus disease in mice and therapeutic intervention with 4'-fluorouridine.

Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses. We used this model to assess the efficacy of the ribonucleoside analog, 4'-fluorouridine (EIDD-2749), and showed that once-daily oral treatment with 3 mg/kg of drug, initiated after the onset of disease, protects mice against lethal MA-HRTV challenge and reduces viral loads in blood and tissues. Our findings provide insights into HRTV virulence and pathogenesis and support further development of EIDD-2749 as a therapeutic intervention for HRTV disease. IMPORTANCE: More than 60 cases of HRTV disease spanning 14 states have been reported to the United States Centers for Disease Control and Prevention. The expanding range of the Lone Star tick that transmits HRTV, the growing population of at-risk persons living in geographic areas where the tick is abundant, and the lack of antiviral treatments or vaccines raise significant public health concerns. Here, we report the development of a new small-animal model of lethal HRTV disease to gain insight into HRTV pathogenesis and the application of this model for the preclinical development of a promising new antiviral drug candidate, EIDD-2749. Our findings shed light on how the virus causes disease and support the continued development of EIDD-2749 as a therapeutic for severe cases of HRTV infection.

Pathological and virological findings of type I interferon receptor knockout mice upon experimental infection with Heartland virus.

Heartland virus (HRTV) causes generalized symptoms, severe shock, and multiple organ failure. We previously reported that interferon-α/ß receptor knockout (IFNAR-/-) mice infected intraperitoneally with 1 × 107 tissue culture-infective dose (TCID50) of HRTV died, while those subcutaneously infected with the same dose of HRTV did not. The pathophysiology of IFNAR-/- mice infected with HRTV and the mechanism underlying the difference in disease severity, which depends on HRTV infection route, were analyzed in this study. The liver, spleen, mesenteric and axillary lymph nodes, and gastrointestinal tract of intraperitoneally (I.P.) infected mice had pathological changes; however, subcutaneously (S.C.) infected mice only had pathological changes in the axillary lymph node and gastrointestinal tract. HRTV RNA levels in the mesenteric lymph node, lung, liver, spleen, kidney, stomach, intestine, and blood were significantly higher in I.P. infected mice than those in S.C. infected mice. Chemokine ligand-1 (CXCL-1), tumor necrosis factor (TNF)-α, interleukin (IL)-12, interferon (IFN)-γ, and IL-10 levels in plasma of I.P. infected mice were higher than those of S.C. infected mice. These results indicated that high levels of viral RNA and the induction of inflammatory responses in HRTV-infected IFNAR-/- mice may be associated with disease severity.

A survey of RNA viruses in mosquitoes from Mozambique reveals novel genetic lineages of flaviviruses and phenuiviruses, as well as frequent flavivirus-like viral DNA forms in Mansonia

Background: Mosquito-borne diseases involving arboviruses represent expanding threats to sub-Saharan Africa imposing as considerable burden to human and veterinary public health. In Mozambique over one hundred species of potential arbovirus mosquito vectors have been identi-fied, although their precise role in maintaining such viruses in circulation in the country remains to be elucidated. The aim of this study was to screen for the presence of flaviviruses, alphaviruses and bunyaviruses in mosquitoes from different regions of Mozambique. Results: Our survey analyzed 14,519 mosquitoes, and the results obtained revealed genetically distinct insectspecific flaviviruses, detected in multiple species of mosquitoes from different genera. In addition, smaller flaviviruslike NS5 sequences, frequently detected in Mansonia seemed to correspond to defective viral sequences, present as viral DNA forms. Furthermore, three lineages of putative members of the Phenuiviridae family were also detected, two of which apparently corresponding to novel viral genetic lineages. Conclusion: This study reports for the first-time novel insect-specific flaviviruses and novel phenuiviruses, as well as frequent flavivirus-like viral DNA forms in several widely known vector species. This unique work represents recent investigation of virus screening conducted in mosquitoes from Mozambique and an important contribution to inform the establishment of a vector control program for arbovirus in the country and in the region.

Our Hantaan Virus Became a New Family, Hantaviridae in the Classification of Order Bunyavirales. It will Remain as a History of Virology

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).

Enfermedad de Schmallenberg: ¿puede afectar al ser humano? / Schmallenberg disease: Can it involve human beings?

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Strategies Against Severe Fever with Thrombocytopenia Syndrome Increasing in Korea / 대한수혈학회지

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease that is caused by the genus phlebovirus in the family Bunyaviridae. The syndrome is characterized by fever, gastrointestinal symptoms, neutropenia, and thrombocytopenia. The number of reported cases and deaths in endemic areas, such as China and Japan, has increased each year. Since the first SFTS patient was identified in 2013, the number of cases have also been increasing every year in South Korea and the disease is posing a great public health concern. The number of patients is increasing and there is a high mortality rate, but there is no established treatment that has proven to be effective. The purpose of this review was to elucidate the various treatment modalities, such as plasma exchange, antiviral agents, e.g. ribavirin, high-dose steroids, and interferon.

Spontaneous Acute Subdural Hemorrhage in a Patient with a Tick Borne Bunyavirus-Induced Severe Fever with Thrombocytopenia Syndrome / 대한신경손상학회지

We report the first case of severe fever with thrombocytopenia syndrome (SFTS) and a spontaneous acute subdural hematoma (SDH) in Korea. A 79-year-old male presented with fever and thrombocytopenia. On the third day of hospitalization, his mental changed from drowsy to semi-coma. Brain computed tomography indicated an acute subdural hemorrhage on the right convexity. He was given early decompressive craniectomy, but did not survive. Real-time reverse transcription polymerase chain reaction analysis of a blood sample indicated the presence of SFTS virus (SFTSV). This is the first reported case with intracranial hemorrhage and SFTS. This case report describes our treatment of a patient with acute SDH and an infection from a tick-borne species of Bunyaviridae.

Development and evaluation of a competitive enzyme-linked immunosorbent assay using a monoclonal antibody for diagnosis of severe fever with thrombocytopenia syndrome virus in bovine sera

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a phlebovirus in the family Bunyaviridae, is an emerging tick-borne infectious disease that impacts humans. This disease manifests as a decreased blood cell count and multi-organ failure, with a case-fatality rate of more than 12% in China. Because vaccines or antiviral drugs for the treatment of this disease are not available, monitoring the SFTS circulation in animals and controlling the tick-mammal cycle are important for preventing SFTS. Monoclonal antibodies against the recombinant nucleoprotein of SFTSV were generated to develop a competitive enzyme-linked immunosorbent assay (cELISA) for the detection of antibodies against SFTSV infection in cattle. The specificity and sensitivity of cELISA was assessed by comparing the results of this assay to those of an immunofluorescence assay (IFA). The results of the cELISA using 416 field bovine serum samples and laboratory-immunized positive sera showed 98.1% consistency with those of the IFA. The cELISA used in this study did not show cross-reactivity with antisera against other viral cattle diseases. The cELISA presented in this study can be applied to detect antibodies against SFTSV in cattle.

Severe Fever with Thrombocytopenia Syndrome Accompanied by Hemophagocytic Lymphohistiocytosis / 대한내과학회지

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease caused by the SFTS virus (family Bunyaviridae, genus Phlebovirus). A 77-year-old female farmer was bitten by a tick and developed a fever 5 days later, resulting in admittance to the emergency room. The laboratory findings showed elevated liver enzyme levels, thrombocytopenia, and leukopenia. Lymphoma was suspected based on computed tomography results. After confirming SFTS virus infection via the polymerase chain reaction, a bone marrow biopsy revealed hemophagocytic lymphohistiocytosis (HLH). HLH is rarely observed in patients with SFTS and few studies have reported the presence of SFTS in bone marrow. Here, we report a case of SFTS that was initially mistaken for a lymphoma, and was accompanied by HLH.

Análise de alterações na expressão de genes relacionados com a imunidade inata em células humanas infectadas com Apeu virus

A família Bunyaviridae consiste em uma das maiores e mais diversificadas famílias de vírus de RNA, contendo cerca de 350 vírus sorologicamente distintos. O Apeu virus (APEUV) é um vírus da família Bunyaviridae que se destaca por seu grande potencial emergente. Isolado pela primeira no Brasil, este vírus pode causar uma doença que apresenta sintomas semelhantes aos da gripe, como febre alta, dor de cabeça e mialgia, associadas geralmente a náuseas, vômitos, fraqueza e fotofobia. Entretanto, apesar de seu potencial patogênico, pouco se sabe sobre a sua interação com o sistema imunológico humano. Com o objetivo de estudar alguns aspectos da resposta imune, principalmente a reposta inata desencadeada pela infecção do APEUV, a expressão de 19 genes (TLR3, TLR7, TLR8, TLR9, MyD88,IRF3, IRF5, IRF7, IRF9, IRAK4, TRAF3, TRAF6, TICAM1, JUN, ROBO-3(RIG-1),IFIH1(MDA-5), IFNα, IFNβ, IFNy) foi analisada. Para tal, foram feitos ensaios de qPCR baseados na metodologia TaqMan®, utilizando cDNA obtido a partir de RNA total extraído de células mononucleares do sangue periférico (PBMC) e de células A549 (linhagem derivada de carcinoma pulmonar humano), infectadas ou não com APEUV por períodos de 4 ou 8 horas.

Como controles, foram utilizadas células infectadas com o vírus da estomatite vesicular (VSV) como controle positivo de uma infecção por vírus de RNA fita simples, e células tratadas com o mock das amostras de vírus como controle negativo. Os dados obtidos foram analisados em software específico. Nossos resultados indicam que PBMC infectadas com APEUV por 4horas (m.o.i.=1 e m.o.i.=3) induzem um aumento na expressão de TLR9 e IFNβ. Quando quantificada a expressão de genes em células A549 infectadas com APEUV(m.o.i.=1 por 4 horas) comparadas com o mock, verificou-se um aumento da expressão dos genes TLR9, IRF3 e IRF7 e no período de 8 horas, também comparando com o mock, verificou-se aumento de forma significativa na expressão de TLR 9, além de um aumento na expressão de TLR3, TLR7, TRAF3 , IRF7 e IFNβ.Verificamos ainda que, após escolher um gene housekeeping através de método estatístico, células A549 infectadas com APEUV em uma m.o.i.=1, tende a aumentara expressão dos genes IFNβ e TICAM-I, fundamentais na indução de um estado celular antiviral. Estudos posteriores são necessários para a determinação dos mecanismos envolvidos na resposta imune inata humana contra o Apeu virus.

Análise de alterações na expressão de genes relacionados com a imunidade inata em células humanas infectadas com Apeu virus / Analysis of changes in the expression of genes related to innate immunity in human cells infected with virus Apeu

A família Bunyaviridae consiste em uma das maiores e mais diversificadas famílias de vírus de RNA, contendo cerca de 350 vírus sorologicamente distintos. O Apeu virus (APEUV) é um vírus da família Bunyaviridae que se destaca por seu grande potencial emergente. Isolado pela primeira no Brasil, este vírus pode causar uma doença que apresenta sintomas semelhantes aos da gripe, como febre alta, dor de cabeça e mialgia, associadas geralmente a náuseas, vômitos, fraqueza e fotofobia. Entretanto, apesar de seu potencial patogênico, pouco se sabe sobre a sua interação com o sistema imunológico humano. Com o objetivo de estudar alguns aspectos da resposta imune, principalmente a reposta inata desencadeada pela infecção do APEUV, a expressão de 19 genes (TLR3, TLR7, TLR8, TLR9, MyD88,IRF3, IRF5, IRF7, IRF9, IRAK4, TRAF3, TRAF6, TICAM1, JUN, ROBO-3(RIG-1),IFIH1(MDA-5), IFNα, IFNβ, IFNy) foi analisada. Para tal, foram feitos ensaios de qPCR baseados na metodologia TaqMan®, utilizando cDNA obtido a partir de RNA total extraído de células mononucleares do sangue periférico (PBMC) e de células A549 (linhagem derivada de carcinoma pulmonar humano), infectadas ou não com APEUV por períodos de 4 ou 8 horas...

Como controles, foram utilizadas células infectadas com o vírus da estomatite vesicular (VSV) como controle positivo de uma infecção por vírus de RNA fita simples, e células tratadas com o mock das amostras de vírus como controle negativo. Os dados obtidos foram analisados em software específico. Nossos resultados indicam que PBMC infectadas com APEUV por 4horas (m.o.i.=1 e m.o.i.=3) induzem um aumento na expressão de TLR9 e IFNβ. Quando quantificada a expressão de genes em células A549 infectadas com APEUV(m.o.i.=1 por 4 horas) comparadas com o mock, verificou-se um aumento da expressão dos genes TLR9, IRF3 e IRF7 e no período de 8 horas, também comparando com o mock, verificou-se aumento de forma significativa na expressão de TLR 9, além de um aumento na expressão de TLR3, TLR7, TRAF3 , IRF7 e IFNβ.Verificamos ainda que, após escolher um gene housekeeping através de método estatístico, células A549 infectadas com APEUV em uma m.o.i.=1, tende a aumentara expressão dos genes IFNβ e TICAM-I, fundamentais na indução de um estado celular antiviral. Estudos posteriores são necessários para a determinação dos mecanismos envolvidos na resposta imune inata humana contra o Apeu virus...

Severe Fever with Thrombocytopenia Syndrome / 대한구급학회지

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease, caused by a novel species of Phlebovirus of Bunyaviridae family, in China, South Korea, and Japan. SFTS is primarily known as a tick-borne disease, and human-to-human transmission is also possible in contact with infectious blood. Common clinical manifestations include fever, thrombocytopenia, and leukopenia as initial symptoms, and multiple organ dysfunction and failure manifest with disease progression. Whereas disease mortality is reported to be 12% to 30% in China, a recent report of cumulative SFTS cases indicated 47% in Korea. Risk factors associated with SFTS were age, presence of neurologic disturbance, serum enzyme levels, and elevated concentrations of certain cytokines. Diagnosis of SFTS is based on viral isolation, viral identification by polymerase chain reaction, and serologic identification of specific immunoglobulin G. Therapeutic guideline has not been formulated, but conservative management is the mainstream of treatment to prevent disease progression and fatal complications.

Genome sequencing and the molecular evolutionary analysis of a SFTSV isolated from Zhejiang province / 中华预防医学杂志

<p><b>OBJECTIVE</b>To sequence the whole genome and to analyze the molecular and evolutionary of Severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) isolated from Zhejiang province.</p><p><b>METHODS</b>Viral RNA was extracted from the specimens and detected by quantitative real-time RT-PCR. SFTSV strain was isolated. A total of 17 overlapping fragments covering the whole genome were amplified by RT-PCR. And the entire genomes were formed by sequencing and assembly the fragments. The SFTSV sequence of Zhejiang strain was compared with the sequences of SFTSV that have been published to generate the phylogenetic tree. And the SFTSV sequence of Zhejiang strain was compared with the sequences of strains of the genus phlebovirus in the Bunyaviridae family and analysis of homology.</p><p><b>RESULTS</b>SFTSV strain was isolated from SFTSV infection positive serum successfully. The genomic fragments were amplified by RT-PCR. A total of 3 cDNA sections were formed by sequencing and assembly the fragments. The S segment contained 1 745 nucleotides. The M fragment contained 3 378 nucleotides, and the L segment contained 6 368 nucleotides. Molecular phylogenetic analysis result showed SFTSV Zhejiang strain had the highest similarity with Japan/SPL004A/2013 strain. The similarity of the S segment was 98%. The similarity of the M fragment was 97%. And it was 98% that of the L fragment. Meanwhile, the comparison results also confirmed the Zhejiang strain belonged to the genus phlebovirus.</p><p><b>CONCLUSION</b>SFTSV Zhejiang strain of isolated from SFTSV infection positive serum successfully. And the genome sequencing was complete molecular evolution analysis shows SFTSV Zhejiang strain has the maximum similarity with SFTSV Japan strain.</p>

Experience of Therapeutic Plasma Exchange in Patients with Severe Fever with Thrombocytopenia Syndrome / 대한수혈학회지

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently issued in northeast Asia and China. The disease is caused by a new phlebovirus in the family Bunyaviridae, severe fever with thrombocytopenia syndrome virus (SFTSV); the transmission vector is believed to be a tick. The number of infections and resulting deaths has been increasing, but there is no effective treatment. METHODS: Clinical and laboratory features of SFTSV-positive patients during the period from May 2013 to October 2014 were reviewed retrospectively using medical records. In cases of patients who underwent therapeutic plasma exchange (TPE), the performance records were also investigated. RESULTS: During the study period, 14 patients were SFTSV-positive. The patients, who ranged in age from 47 to 82, had mostly outdoor activities before admission. The major symptoms included high fever, myalgia, and gastrointestinal symptoms. Laboratory findings showed decreased white blood cell (WBC), neutrophils and platelets and elevated activated partial thromboplastin time (aPTT), aspartate aminotransferase (AST), lactate dehydrogenase (LD), and creatine phosphokinase (CK). Two patients died during the study period, however, nine patients who received TPE showed improvement. CONCLUSION: We suppose that TPE can be used for treatment of serious SFTS and gives the effect of reducing the fatality rate.

Four Cases of Severe Fever with Thrombocytopenia Syndrome Occurring in Jeju / 대한피부과학회지

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel SFTS bunyavirus (SFTSV), a member of the genus Phlebovirus in the family Bunyaviridae. SFTSV is believed to be transmitted by Haemaphysalis longicornis. Common symptoms of SFTS include high fever, vomiting, diarrhea, thrombocytopenia, leukocytopenia, and multi-organ failure with an average case-fatality rate of 12~30%. In 2009, SFTS was firstly reported in China. In 2013, 27 cases of SFTS were documented in Korea, and 6 cases were confirmed on Jeju Island. Although the pathogenesis and transmission mode of SFTS remain unclear, SFTS is now considered endemic in East Asia. Accordingly, SFTS needs to be differentiated from scrub typhus, leptospirosis, and hemorrhagic fever with renal syndrome. We here report 4 cases of SFTS preceded by a tick bite, which were in need of a differential diagnosis of scrub typhus.

A double antibody sandwich ELISA based assay for titration of severe fever with thrombocytopenia syndrome virus / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To develop an assay for titration of severe fever with thrombocytopenia syndrome virus (SFTSV) based on double antibody sandwich ELISA.</p><p><b>METHODS</b>A double antibody sandwich ELISA was developed for detection of SFTSV based on SFTSV nucleocapsid (N) protein specific poly- and monoclonal antibodies, procedures were optimized and evaluated. This ELISA based titration assay was compared with fluorescence assasy and plaque assay based titration method.</p><p><b>RESULTS</b>The results suggested that the titers obtained by ELISA based method are consistent with those obtained by IFA based method (R = 0.999) and the plaque assay titration method (R = 0.949).</p><p><b>CONCLUSION</b>The novel ELISA based titration method with high sensitivity and specificity is easy to manage and perform, and can overcome the subjectivity associated with result determination of the fluorescence assay and plaque assay based methods. The novel ELISA based titration method can also be applied to high throughput detection.</p>

Subcellular localization of severe fever with thrombocytopenia syndrome virus in macrophages / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To study the subcellular localization of severe fever with thrombocytopenia syndrome virus (SFTSV) in macrophages and understand the replication and assembly mechanism of SFTSV in host cells.</p><p><b>METHODS</b>Using two types of human macrophage cell lines THP-1 and U937, the study analyzed the intracellular colocalization of SFTSV with Golgi apparatus and endoplasmic reticulum by immunefluorescence staining and confocal microscopy.</p><p><b>RESULTS</b>SFTSV infected macrophage cell lines THP-1 and U937. Immunofluorescence staining showed that the SFTSV nuclear protein colocalized with Golgi apparatus and closely surrounded by endoplasmic reticulum in the perinuclear region.</p><p><b>CONCLUSION</b>The results suggested that Golgi complex and endoplasmic reticulum are probably the sites for formation and maturation of SFTSV viral particles.</p>

Severe Fever with Thrombocytopenia Syndrome Virus, Crimean-Congo Haemorrhagic Fever Virus, and Migratory Birds

Severe Fever with Thrombocytopenia Syndrome (SFTS) and Crimean-Congo Haemorrhagic Fever (CCHF) are tick-borne diseases belonging to the family Bunyaviridae. Since SFTS was first reported in China in 2009, the virus was isolated and confirmed in 2011, with additional reports of SFTSV expanding its geographic range from China to South Korea and Japan. CCHFV has the widest geographic distribution of any tick-borne virus, encompassing around 30 countries from eastern China through Asia, the Middle East, and southeastern Europe to Africa. During the past decade, CCHFV has emerged in new areas of Europe, Africa, the Middle East, and Asia and has increased in endemic areas. Migratory birds are considered to play a role in dispersing CCHFV vectors, and the virus. This review summarises SFTSV and CCHFV, highlighting the role of migratory birds in the transmission of tick-borne disease.