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1.
Nat Commun ; 15(1): 1121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321047

RESUMO

The first step in disease pathogenesis for arboviruses is the establishment of infection following vector transmission. For La Crosse virus (LACV), the leading cause of pediatric arboviral encephalitis in North America, and other orthobunyaviruses, the initial course of infection in the skin is not well understood. Using an intradermal (ID) model of LACV infection in mice, we find that the virus infects and replicates nearly exclusively within skin-associated muscle cells of the panniculus carnosus (PC) and not in epidermal or dermal cells like most other arbovirus families. LACV is widely myotropic, infecting distal muscle cells of the peritoneum and heart, with limited infection of draining lymph nodes. Surprisingly, muscle cells are resistant to virus-induced cell death, with long term low levels of virus release progressing through the Golgi apparatus. Thus, skin muscle may be a key cell type for the initial infection and spread of arboviral orthobunyaviruses.


Assuntos
Arbovírus , Infecções por Bunyaviridae , Encefalite da Califórnia , Vírus La Crosse , Orthobunyavirus , Humanos , Criança , Animais , Camundongos , Replicação Viral , Músculos
2.
Arch Virol ; 169(3): 40, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38308735

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been approved for use against SFTS. Antibody drugs have shown promise in treating lethal infectious diseases that currently have no established treatments. In the case of SFTS, however, only a limited amount of research has been done on SFTSV-neutralizing antibodies targeting the transmembrane proteins Gn and Gc, which play critical roles in viral infection. This study focuses on the production and characterization of antibodies targeting the SFTSV Gc protein. Monoclonal antibodies against Gc were generated through immunization of mice, and their antiviral activity was evaluated. Three out of four anti-Gc antibody clones from this study demonstrated dose-dependent SFTSV neutralization activity, two of which exhibited a synergistic effect on the neutralization activity of the anti-Gn antibody clone Mab4-5. Further studies are necessary to identify key sites on the SFTSV glycoprotein and to develop novel agents as well as antibodies with diverse mechanisms of action against SFTSV.


Assuntos
Infecções por Bunyaviridae , Febres Hemorrágicas Virais , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Camundongos , Glicoproteínas
3.
EMBO Mol Med ; 16(3): 575-595, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38366162

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective therapies or vaccines available, understanding the disease's mechanisms is crucial. Recent studies found increased expression of programmed cell death-1 (PD-1) on dysfunctional T cells in SFTS patients. However, the role of the PD-1/programmed cell death-ligand 1 (PD-L1) pathway in SFTS progression remains unclear. We investigated PD-1 blockade as a potential therapeutic strategy against SFTSV replication. Our study analyzed clinical samples and performed in vitro experiments, revealing elevated PD-1/PD-L1 expression in various immune cells following SFTSV infection. An anti-PD-1 nanobody, NbP45, effectively inhibited SFTSV infection in peripheral blood mononuclear cells (PBMCs), potentially achieved through the mitigation of apoptosis and the augmentation of T lymphocyte proliferation. Intriguingly, subcutaneous administration of NbP45 showed superior efficacy compared to a licensed anti-PD-1 antibody in an SFTSV-infected humanized mouse model. These findings highlight the involvement of the PD-1/PD-L1 pathway during acute SFTSV infection and suggest its potential as a host target for immunotherapy interventions against SFTSV infection.


Assuntos
Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Humanos , Camundongos , Infecções por Bunyaviridae/tratamento farmacológico , Phlebovirus/fisiologia , Antígeno B7-H1 , Leucócitos Mononucleares , Receptor de Morte Celular Programada 1
4.
Viruses ; 16(2)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38400069

RESUMO

Orthobunyaviruses (order Bunyavirales, family Peribunyaviridae) in the Simbu serogroup have been responsible for widespread epidemics of congenital disease in ruminants. Australia has a national program to monitor arboviruses of veterinary importance. While monitoring for Akabane virus, a novel orthobunyavirus was detected. To inform the priority that should be given to this detection, a scoping review was undertaken to (1) characterise the associated disease presentations and establish which of the Simbu group viruses are of veterinary importance; (2) examine the diagnostic assays that have undergone development and validation for this group of viruses; and (3) describe the methods used to monitor the distribution of these viruses. Two search strategies identified 224 peer-reviewed publications for 33 viruses in the serogroup. Viruses in this group may cause severe animal health impacts, but only those phylogenetically arranged in clade B are associated with animal disease. Six viruses (Akabane, Schmallenberg, Aino, Shuni, Peaton, and Shamonda) were associated with congenital malformations, neurological signs, and reproductive disease. Diagnostic test interpretation is complicated by cross-reactivity, the timing of foetal immunocompetence, and sample type. Serological testing in surveys remains a mainstay of the methods used to monitor the distribution of SGVs. Given significant differences in survey designs, only broad mean seroprevalence estimates could be provided. Further research is required to determine the disease risk posed by novel orthobunyaviruses and how they could challenge current diagnostic and surveillance capabilities.


Assuntos
Infecções por Bunyaviridae , Doenças dos Bovinos , Orthobunyavirus , Vírus Simbu , Bovinos , Animais , Gado , Infecções por Bunyaviridae/diagnóstico , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/veterinária , Estudos Soroepidemiológicos , Sorogrupo , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/epidemiologia , Testes Diagnósticos de Rotina
5.
J Med Virol ; 96(3): e29491, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38402626

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne hemorrhagic fever disease with high fatality rate of 10%-20%. Vaccines or specific therapeutic measures remain lacking. Human interferon inducible transmembrane protein 3 (hIFITM3) is a broad-spectrum antiviral factor targeting viral entry. However, the antiviral activity of hIFITM3 against SFTS virus (SFTSV) and the functional mechanism of IFITM3 remains unclear. Here we demonstrate that endogenous IFITM3 provides protection against SFTSV infection and participates in the anti-SFTSV effect of type Ⅰ and Ⅲ interferons (IFNs). IFITM3 overexpression exhibits anti-SFTSV function by blocking Gn/Gc-mediated viral entry and fusion. Further studies showed that IFITM3 binds SFTSV Gc directly and its intramembrane domain (IMD) is responsible for this interaction and restriction of SFTSV entry. Mutation of two neighboring cysteines on IMD weakens IFITM3-Gc interaction and attenuates the antiviral activity of IFITM3, suggesting that IFITM3-Gc interaction may partly mediate the inhibition of SFTSV entry. Overall, our data demonstrate for the first time that hIFITM3 plays a critical role in the IFNs-mediated anti-SFTSV response, and uncover a novel mechanism of IFITM3 restriction of SFTSV infection, highlighting the potential of clinical intervention on SFTS disease.


Assuntos
Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Proteínas Virais/metabolismo , Internalização do Vírus , Phlebovirus/genética , Antivirais/uso terapêutico , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/genética
8.
J Virol ; 98(3): e0169823, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38358288

RESUMO

Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne virus of the Orthonairovirus genus, persistently infects tick cells. It has been reported to establish persistent infection in non-human primates, but virological analysis has not yet been performed in human cells. Here, we investigated whether and how nairoviruses persistently infect human cells using Hazara orthonairovirus (HAZV), a surrogate model for CCHFV. We established a human cell line that was persistently infected with HAZV. Surprisingly, virions of persistently infected HAZV (HAZVpi) were not observed in the culture supernatants. There were five mutations (mut1, mut2, mut3, mut4, and mut5) in L protein of HAZVpi. Mutations in L protein of HAZVpi contribute to non-detection of virion in the supernatants. Lmut4 was found to cause low viral growth rate, despite its high polymerase activity. The low growth rate was restored by Lmut2, Lmut3, and Lmut5. The polymerase activity of Lmut1 was extremely low, and recombinant HAZV carrying Lmut1 (rHAZV/Lmut1) was not released into the supernatants. However, genomes of rHAZV/Lmut1 were retained in the infected cells. All mutations (Lmut1-5) found in L protein of HAZVpi were required for experimental reproduction of HAZVpi, and only Lmut1 and Lmut4 were insufficient. We demonstrated that point mutations in viral polymerase contribute to the establishment of persistent HAZV infection. Furthermore, innate immunity was found to be suppressed in HAZVpi-infected cells, which also potentially contributes to viral persistence. This is the first presentation of a possible mechanism behind how nairoviruses establish persistent infection in human cells. IMPORTANCE: We investigated whether and how nairoviruses persistently infect human cells, using Hazara orthonairovirus (HAZV), a surrogate model for Crimean-Congo hemorrhagic fever virus. We established a human cell line that was persistently infected with HAZV. Five mutations were found in L protein of persistently infected HAZV (HAZVpi): mut1, mut2, mut3, mut4, and mut5. Among them, Lmut1 and Lmut4 restricted viral growth by low polymerase activity and low growth rate, respectively, leading to inhibition of viral overgrowth. The restriction of viral growth caused by Lmut1 and Lmut4 was compensated by other mutations, including Lmut2, Lmut3, and Lmut5. Each of the mutations found in L protein of HAZVpi was concluded to cooperatively modulate viral growth, which facilitates the establishment of persistent infection. Suppression of innate immunity also potentially contributes to virus persistence. This is the first presentation of a possible mechanism behind how nairoviruses establish persistent infection in human cells.


Assuntos
Infecções por Bunyaviridae , Nairovirus , Animais , Humanos , Linhagem Celular , Vírus da Febre Hemorrágica da Crimeia-Congo/fisiologia , Febre Hemorrágica da Crimeia/virologia , Mutação , Nairovirus/genética , Infecção Persistente , Infecções por Bunyaviridae/virologia
10.
Ticks Tick Borne Dis ; 15(2): 102307, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38194758

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a crucial role in the defense against SFTSV; however, the impact of viral propagation of STFSV on the innate immune system remains unclear. Although proteomics analysis revealed that the expression of the downregulator of transcription 1 (DR1) increased after SFTSV infection, the specific change trend and the functional role of DR1 during viral infection remain unelucidated. In this study, we demonstrate that DR1 was highly expressed in response to SFTSV infection in HEK 293T cells using qRT-PCR and Western blot analysis. Furthermore, viral replication significantly increased the expression of various TLRs, especially TLR9. Our data indicated that DR1 positively regulated the expression of TLRs in HEK 293T cells, DR1 overexpression highly increased the expression of numerous TLRs, whereas RNAi-mediated DR1 silencing decreased TLR expression. Additionally, the myeloid differentiation primary response gene 88 (MyD88)-dependent or TIR-domain-containing adaptor inducing interferon-ß (TRIF)-dependent signaling pathways were highly up- and downregulated by the overexpression and silencing of DR1, respectively. Finally, we report that DR1 stimulates the expression of TLR7, TLR8, and TLR9, thereby upregulating the TRIF-dependent and MyD88-dependent signaling pathways during the SFTSV infection, attenuating viral replication, and enhancing the production of type I interferon and various inflammatory factors, including IL-1ß, IL-6, and IL-8. These results imply that DR1 defends against SFTSV replication by inducing the expression of TLR7, TLR8, and TLR9. Collectively, our findings revealed a novel role and mechanism of DR1 in mediating antiviral responses and innate immunity.


Assuntos
Infecções por Bunyaviridae , Phlebovirus , Fosfoproteínas , Transdução de Sinais , Fatores de Transcrição , Animais , Humanos , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Regulação para Baixo , Células HEK293 , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fosfoproteínas/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor 8 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Fatores de Transcrição/metabolismo , Phlebovirus/fisiologia , Infecções por Bunyaviridae/imunologia , Infecções por Bunyaviridae/metabolismo , Infecções por Bunyaviridae/virologia
11.
Virus Res ; 341: 199318, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38224842

RESUMO

The Oropouche virus is an important arthropod-borne virus in the Peribunyaviridae family that can cause febrile illnesses, and it is widely distributed in tropical regions such as Central and South America. Since the virus was first identified, a large number of related cases are reported every year. No deaths have been reported to date, however, the virus can cause systemic infections, including the nervous and blood systems, leading to serious complications. The transmission of Oropouche virus occurs through both urban and sylvatic cycles, with the anthropophilic biting midge Culicoides paraensis serving as the primary vector in urban areas. Direct human-to-human transmission of Oropouche virus has not been observed. Oropouche virus consists of three segments, and the proteins encoded by the different segments enables the virus to replicate efficiently in the host and to resist the host's immune response. Phylogenetic analyses showed that Oropouche virus sequences are geographically distinct and have closer homologies with Iquitos virus and Perdoes virus, which belong to the family Peribunyaviridae. Despite the enormous threat it poses to public health, there are currently no licensed vaccines or specific antiviral treatments for the disease it causes. Recent studies have utilised imJatobal virusmunoinformatics approaches to develop epitope-based peptide vaccines, which have laid the groundwork for the clinical use of vaccines. The present review focuses on the structure, epidemiology, immunity and phylogeny of Oropouche virus, as well as the progress of vaccine development, thereby attracting wider attention and research, particularly with regard to potential vaccine programs.


Assuntos
Arbovírus , Infecções por Bunyaviridae , Orthobunyavirus , Vacinas , Humanos , Filogenia , Orthobunyavirus/genética , Infecções por Bunyaviridae/epidemiologia
12.
J Vet Med Sci ; 86(2): 211-220, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38171741

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonotic disease, endemic to Asian regions, including western Japan. Cats appear to suffer a particularly severe form of the disease; however, feline SFTS is not clinically well characterized. Accordingly, in this study, we investigated the associations of, demographic, hematological and biochemical, immunological, and virological parameters with clinical outcome (fatal cases vs. survivors) in SFTSV-positive cats. Viral genomic analysis was also performed. Viral load in blood, total bilirubin, creatine phosphokinase, serum amyloid A, interleukin-6, tumor necrotic factor-α, and virus-specific IgM and IgG differed significantly between survivors and fatal cases, and thus may have utility as prognosticators. Furthermore, survivor profiling revealed high-level of viremia with multiple parameters (white blood cells, platelet, total bilirubin, glucose, and serum amyloid A) beyond the reference range in the 7-day acute phase, and signs of clinical recovery in the post-acute phase (parameters returning to, or tending toward, the reference range). However, SFTSV was still detectable from some survived cats even 14 days after onset of disease, indicating the risk of infection posed by close-contact exposure may persist through the post-acute phase. This study provides useful information for prognostic assessments of acute feline SFTS, and may contribute to early treatment plans for cats with SFTS. Our findings also alert pet owners and animal health professionals to the need for prolonged vigilance against animal-to-human transmission when handling cats that have been diagnosed with SFTS.


Assuntos
Infecções por Bunyaviridae , Doenças do Gato , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Doenças Transmitidas por Carrapatos , Animais , Humanos , Gatos , Febre Grave com Síndrome de Trombocitopenia/veterinária , Prognóstico , Phlebovirus/genética , Infecções por Bunyaviridae/veterinária , Infecções por Bunyaviridae/epidemiologia , Proteína Amiloide A Sérica , Doenças Transmitidas por Carrapatos/veterinária , Bilirrubina
13.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(1): 112-116, 2024 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-38228532

RESUMO

Objective: To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China. Methods: The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed. Results: From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age. Conclusion: From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.


Assuntos
Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Pessoa de Meia-Idade , Humanos , Feminino , Masculino , Trombocitopenia/epidemiologia , Febre/epidemiologia , China/epidemiologia , Incidência , Infecções por Bunyaviridae/epidemiologia
14.
Vet Res Commun ; 48(1): 449-457, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37831381

RESUMO

Akabane virus (AKAV) is known as a major teratogenic agent of ruminant fetuses. In this study, we investigated the relationship between porcine abnormal deliveries and AKAV by serology, pathology, and virology investigations using specimens from 16 stillborn fetuses delivered in southern Japan between 2013 and 2015. The major clinical manifestations in stillborn fetuses were hydranencephaly, arthrogryposis, spinal curvature, and both skeletal muscle and subcutaneous edema. Histologic examination of the specimens identified atrophy of skeletal muscle fibers accompanied by adipose replacement. Nonsuppurative encephalomyelitis and decreased neuronal density in the ventral horn of the spinal cord were shown in two separate fetuses, respectively. Neutralizing antibody titers to AKAV were detected in most of the tested fetuses (13/16). The AKAV sequences detected in the affected fetuses in 2013 and 2015 were highly identical and closely related to Japanese AKAV isolates which were isolated in 2013 and sorted into genogroup I of AKAV. Immunohistochemistry visualized AKAV antigens in the neuronal cells of the central nervous system of the fetuses. These findings indicate that AKAV was involved in the birth of abnormal piglets at the affected farm. The clinical manifestations and histopathological features in the stillborn fetuses were very similar to those in ruminant neonates affected by AKAV. To avoid misdiagnosis and to evaluate the precise impact of AKAV on pig reproduction, AKAV should be considered in differential diagnoses of reproductive failures in pigs.


Assuntos
Infecções por Bunyaviridae , Orthobunyavirus , Doenças dos Suínos , Animais , Infecções por Bunyaviridae/diagnóstico , Infecções por Bunyaviridae/veterinária , Infecções por Bunyaviridae/patologia , Feto/patologia , Japão/epidemiologia , Ruminantes , Suínos , Doenças dos Suínos/diagnóstico
15.
Virol Sin ; 39(1): 113-122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38008382

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. However, the viral-host interaction of SFTSV remains largely unknown. The heat-shock protein 90 (Hsp90) family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses. Here, we showed that Hsp90 is an important host factor involved in SFTSV infection. Hsp90 inhibitors significantly reduced SFTSV replication, viral protein expression, and the formation of inclusion bodies consisting of nonstructural proteins (NSs). Among viral proteins, NSs appeared to be the most reduced when Hsp90 inhibitors were used, and further analysis showed that their translation was affected. Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90 ß specifically interacted with them. Knockdown of Hsp90 ß expression also inhibited replication of SFTSV. These results suggest that Hsp90 ß plays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.


Assuntos
Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Febre Grave com Síndrome de Trombocitopenia/genética , Phlebovirus/genética , Interações entre Hospedeiro e Microrganismos
16.
Ticks Tick Borne Dis ; 15(1): 102277, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37981467

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS cases have been identified in mountainous and hilly areas, with a few in island areas. In this study, we conducted a systematic investigation about natural infection of SFTS virus (SFTSV) among humans, animals and ticks in a coastal endemic prefecture, containing island, plains and mountain settings, in Zhejiang Province, Southeastern China. From July 2020 to June 2021, 1117 participants completed a survey with questionnaire interview and serum testing. Meanwhile, 862 serum samples of domestic animals, 275 spleen tissue samples of wild animals and 829 ticks representing five species (predominantly Haemaphysalis longicornis and Rhipicephalus sanguineus sensu lato) were collected. The seroprevalence of anti-SFTSV total antibody and IgM antibody among the participants was 4.8 % (54/1117) and 0.6 % (7/1117), respectively. Multivariate logistic regression analysis indicated that living in the island area (OR=2.66; 95 %CI: 1.04-6.80; P = 0.041) was significantly associated with seropositivity of total antibody to SFTSV. Furthermore, a higher seroprevalence was observed in domestic animals (36.1 %), while the SFTSV-RNA infection rate was 0.4 % in wild animals and the minimum infection rate (MIR) was 0.8 % for all tick species combined. The only tick species infected with SFTSV was H. longicornis. The prevalence of SFTSV infection in the island area, manifested by anti-SFTSV total antibody (P = 0.012) and IgM antibody (P = 0.004) among humans, anti-SFTSV total antibody (P<0.001) among domestic animals, and SFTSV-RNA among ticks (P = 0.022), was significantly higher than that in the mountainous area and the plain area. Furthermore, phylogenetic analysis showed that SFTSV sequences obtained from ticks in the island area were clustered with reported strains in Japan and South Korea. These results suggest that islands in the study area might be an important natural focus of SFTSV.


Assuntos
Infecções por Bunyaviridae , Phlebovirus , Rhipicephalus sanguineus , Febre Grave com Síndrome de Trombocitopenia , Animais , Humanos , Filogenia , Estudos Soroepidemiológicos , Phlebovirus/genética , Animais Domésticos , Animais Selvagens , China/epidemiologia , RNA , Rhipicephalus sanguineus/genética , Imunoglobulina M , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/veterinária
17.
J Vet Med Sci ; 86(2): 228-238, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38143087

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a tick-borne virus called severe fever with thrombocytopenia syndrome virus (SFTSV). In recent years, human infections through contact with ticks and through contact with the bodily fluids of infected dogs and cats have been reported; however, no vaccine is currently available. SFTSV has two glycoproteins (Gn and Gc) on its envelope, which are vaccine-target antigens involved in immunogenicity. In the present study, we constructed novel SFTS vaccine candidates using an adeno-associated virus (AAV) vector to transport the SFTSV glycoprotein genome. AAV vectors are widely used in gene therapy and their safety has been confirmed in clinical trials. Recently, AAV vectors have been used to develop influenza and SARS-CoV-2 vaccines. Two types of vaccines (AAV9-SFTSV Gn and AAV9-SFTSV Gc) carrying SFTSV Gn and Gc genes were produced. The expression of Gn and Gc proteins in HEK293T cells was confirmed by infection with vaccines. These vaccines were inoculated into mice, and the collected sera produced anti-SFTS antibodies. Furthermore, sera from AAV9-SFTSV Gn infected mice showed a potent neutralizing ability, similar to previously reported SFTS vaccine candidates that protected animals from SFTSV infection. These findings suggest that this vaccine is a promising candidate for a new SFTS vaccine.


Assuntos
Infecções por Bunyaviridae , Doenças do Gato , Doenças do Cão , Phlebovirus , Doenças dos Roedores , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Animais , Humanos , Gatos , Camundongos , Cães , Febre Grave com Síndrome de Trombocitopenia/veterinária , Dependovirus/genética , Dependovirus/metabolismo , Phlebovirus/genética , Infecções por Bunyaviridae/veterinária , Vacinas contra COVID-19 , Células HEK293 , Glicoproteínas , Trombocitopenia/veterinária
18.
Arch Virol ; 169(1): 7, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082138

RESUMO

Akabane virus (AKAV) is a member of the genus Orthobunyavirus, family Peribunyaviridae. In addition to AKAV strains that cause fetal Akabane disease, which is characterized by abortion in ruminants, some AKAV strains cause postnatal infection characterized by nonsuppurative encephalomyelitis in ruminants. Here, we focused on the NSs protein, a virulence factor for most viruses belonging to the genus Orthobunyavirus, and we hypothesized that this protein would act as a neurovirulence factor in AKAV strains causing postnatal encephalomyelitis. We generated AKAV strains that were unable to produce the NSs protein, derived from two different genogroups, genogroups I and II, and then examined the role of their NSs proteins by inoculating mice intracerebrally with these modified viruses. Our results revealed that the neurovirulence of genogroup II strains is dependent on the NSs protein, whereas that of genogroup I strains is independent of this protein. Notably, infection of primary cultured bovine cells with these viruses suggested that the NSs proteins of both genogroups suppress innate immune-related gene expression with equal efficiency. These results indicate differences in the determinants of virulence of orthobunyaviruses.


Assuntos
Infecções por Bunyaviridae , Encefalomielite , Orthobunyavirus , Gravidez , Feminino , Bovinos , Animais , Camundongos , Infecções por Bunyaviridae/veterinária , Orthobunyavirus/genética , Genótipo , Ruminantes
19.
Front Cell Infect Microbiol ; 13: 1298050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106473

RESUMO

Objective: The study aimed to comprehensively describe and evaluate the pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients with co-infections. Methods: We retrospectively collected clinical data and laboratory indicators of the SFTS patients at Tongji Hospital from October 2021 to July 2023. Results: A total of 157 patients with SFTS virus (SFTSV) infection were involved in the analysis, including 43 co-infection and 114 non-co-infection patients. The pathogens responsible for co-infection were primarily isolated from respiratory specimens. Fungal infections, primarily Aspergillus fumigatus, were observed in 22 cases. Bacterial infections, with Klebsiella pneumoniae and carbapenem-resistant Acinetobacter baumannii as the main pathogens, were identified in 20 cases. SFTS patients with co-infection exhibited higher mortality (P=0.011) compared to non-co-infection patients. Among SFTS patients co-infected with both bacteria and fungi (8 cases) or specific drug-resistant strains (11 cases), the mortality rate was as high as 70% (14/19). In comparison with the non-co-infection group, SFTS patients with co-infection displayed significant alteration in inflammatory markers, coagulation function, and liver function indicators. Conclusion: The mortality rate of SFTS patients with co-infection is relatively high, underscoring the need for enhanced monitoring and timely, appropriate treatment to minimize the mortality rate.


Assuntos
Infecções por Bunyaviridae , Coinfecção , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Humanos , Estudos Retrospectivos , Infecções por Bunyaviridae/complicações , Infecções por Bunyaviridae/diagnóstico , Infecções por Bunyaviridae/epidemiologia , Trombocitopenia/complicações , Trombocitopenia/diagnóstico
20.
Viruses ; 15(12)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38140579

RESUMO

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the SFTS Virus (SFTSV), is a global health threat. SFTSV in Taiwan has only been reported in ruminants and wild animals. Thus, we aimed to investigate the infection statuses of dogs and cats, the animals with closer human interactions. Overall, the SFTSV RNA prevalence was 23% (170/735), with dogs showing a 25.9% (111/429) prevalence and cats at 19.3% (59/306) prevalence. Noticeably, the prevalence in stray animals (39.8% 77/193) was significantly higher than in domesticated ones (17.2%, 93/542). Among the four categories analyzed, the highest SFTSV prevalence was found in the stray dogs at 53.9% (120/193), significantly higher than the 24.2% prevalence noted in stray cats. In contrast, domesticated animals exhibited similar prevalence rates, with 17.1% for dogs and 17.2% for cats. It is noteworthy that in the domesticated animal groups, a significantly elevated prevalence (45%, 9/20) was observed among cats exhibiting thrombocytopenia compared to those platelet counts in the reference range (4.8%, 1/21). The high infection rate in stray animals, especially stray dogs, indicated that exposure to various outdoor environments influences the prevalence of infections. Given the higher human interaction with dogs and cats, there is a need for proactive measures to reduce the risk associated with the infection of SFTSV in both animals and humans.


Assuntos
Infecções por Bunyaviridae , Doenças do Gato , Doenças do Cão , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Gatos , Humanos , Cães , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/veterinária , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/veterinária , Taiwan/epidemiologia , Doenças do Gato/epidemiologia , Doenças do Cão/epidemiologia , Phlebovirus/genética , Animais Selvagens , Animais Domésticos
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