-
Viruses Nov 2023Mudanjiang phlebovirus (MJPV) is a newly discovered phlebovirus, initially detected from ticks in China in 2022. In this study, by next-generation sequencing (NGS) on a...
Mudanjiang phlebovirus (MJPV) is a newly discovered phlebovirus, initially detected from ticks in China in 2022. In this study, by next-generation sequencing (NGS) on a wide variety of ticks and wild small animals in China, we detected MJPV from and . Additionally, we conducted RT-PCR and sequencing on 1815 adult ticks and 805 wild small mammals collected from eight provinces in China between 2017 and 2021. MJPV RNA-positive results were found in 0.22% (4/1815) of tick samples, as well as in 0.12% (1/805) of rodent samples. All positive detections were obtained from Heilongjiang and Inner Mongolia. Sequencing analysis revealed nucleotide similarities ranging from 98.23% to 99.11%, as well as amino acid similarities ranging from 99.12% to100%, between the current MJPV strain and previously reported strains of MJPV. Phylogenetic tree analysis demonstrated that the previously reported MJPV strain along with our two variants clustered together with other tick-borne phenuiviruses, indicating their close relationship within this viral group. This study represents the first detection of MJPV infection in wild rodents, expanding the known host range for this virus in the endemic regions.
Topics: Animals; Phlebovirus; Phylogeny; Ixodes; Animals, Wild; Viruses; Rodentia; China
PubMed: 38140594
DOI: 10.3390/v15122353 -
Virology Journal Jul 2016Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift... (Review)
Review
Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.
Topics: Animals; Apoptosis; Humans; Interferon-beta; Rift Valley Fever; Rift Valley fever virus; Viral Nonstructural Proteins
PubMed: 27368371
DOI: 10.1186/s12985-016-0573-8 -
International Journal of Infectious... May 2023To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may...
OBJECTIVES
To determine whether glucocorticoids can improve clinical outcomes of severe fever with thrombocytopenia syndrome (SFTS) patients, and how to identify patients who may benefit from the treatment.
METHODS
A retrospective study was performed to include patients with confirmed SFTS from designated hospitals. The effect of glucocorticoids in reducing case fatality rate (CFR) and improving clinical recovery was evaluated by multivariate logistic regression models.
RESULTS
A total of 2478 eligible patients were analyzed, of whom 331 received glucocorticoids. An integrated parameter (L-index) based on Log(lactate dehydrogenase*blood urea nitrogen/lymphocyte count) was constructed to discriminate disease severity. In patients with L-index >3.823 indicating severe SFTS, significantly reduced CFR was observed in patients receiving low-moderate glucocorticoid doses with ≤60 mg daily methylprednisolone or equivalent (odds ratio [OR] 0.46, 95% confidence interval [CI], 0.23-0.88), but not in patients receiving high doses. In patients with L-index ≤3.823 indicating mild SFTS, glucocorticoid treatment was significantly associated with increased CFR (OR 3.34, 95% CI, 1.35-9.51), and mainly attributable to high-dose glucocorticoids (OR 2.83, 95% CI, 1.72-4.96). Disaggregated data analysis revealed a significant effect only in patients ≤65 years old, male, and early admission within 7 days after onset, but not in their counterparts.
CONCLUSION
Glucocorticoids are not recommended for mild patients defined by L-index <3.823; however, patients with severe SFTS may benefit from low-moderate doses of glucocorticoids.
Topics: Humans; Male; Aged; Severe Fever with Thrombocytopenia Syndrome; Retrospective Studies; Phlebovirus; Glucocorticoids; Critical Illness; Treatment Outcome
PubMed: 36921682
DOI: 10.1016/j.ijid.2023.03.015 -
The Journal of Biological Chemistry Jan 2018Regulated mRNA decay plays a vital role in determining both the level and quality of cellular gene expression. Viral RNAs must successfully evade this host RNA decay...
Regulated mRNA decay plays a vital role in determining both the level and quality of cellular gene expression. Viral RNAs must successfully evade this host RNA decay machinery to establish a productive infection. One way for RNA viruses to accomplish this is to target the cellular exoribonuclease XRN1, because this enzyme is accessible in the cytoplasm and plays a major role in mRNA decay. Members of the Flaviviridae use RNA structures in their 5'- or 3'-untranslated regions to stall and repress XRN1, effectively stabilizing viral RNAs while also causing significant dysregulation of host cell mRNA stability. Here, we use a series of biochemical assays to demonstrate that the 3'-terminal portion of the nucleocapsid (N) mRNA of Rift Valley fever virus, a phlebovirus of the Bunyaviridae family, also can effectively stall and repress XRN1. The region responsible for impeding XRN1 includes a G-rich portion that likely forms a G-quadruplex structure. The 3'-terminal portions of ambisense-derived transcripts of multiple arenaviruses also stalled XRN1. Therefore, we conclude that RNAs from two additional families of mammalian RNA viruses stall and repress XRN1. This observation. emphasizes the importance and commonality of this viral strategy to interfere with the 5'-to-3'-exoribonuclease component of the cytoplasmic RNA decay machinery.
Topics: 3' Untranslated Regions; Exoribonucleases; HEK293 Cells; HeLa Cells; Host-Pathogen Interactions; Humans; Microtubule-Associated Proteins; Phlebovirus; RNA Stability; RNA, Messenger; RNA, Viral; Rift Valley fever virus; Sequence Analysis, RNA
PubMed: 29118186
DOI: 10.1074/jbc.M117.805796 -
Viruses Aug 2019We screened ticks and human clinical specimens to detect and characterize tick phleboviruses and pathogenicity in vertebrates. Ticks were collected at locations in...
We screened ticks and human clinical specimens to detect and characterize tick phleboviruses and pathogenicity in vertebrates. Ticks were collected at locations in Istanbul (Northwest Anatolia, Thrace), Edirne, Kırklareli, and Tekirdağ (Thrace), Mersin (Mediterranean Anatolia), Adiyaman and Şanlıurfa (Southeastern Anatolia) provinces from 2013-2018 and were analyzed following morphological identification and pooling. Specimens from individuals with febrile disease or meningoencephalitic symptoms of an unknown etiology were also evaluated. The pools were screened via generic tick phlebovirus amplification assays and products were sequenced. Selected pools were used for cell culture and suckling mice inoculations and next generation sequencing (NGS). A total of 7492 ticks were screened in 609 pools where 4.2% were positive. A phylogenetic sequence clustering according to tick species was observed. No human samples were positive. NGS provided near-complete viral replicase coding sequences in three pools. A comprehensive analysis revealed three distinct, monophyletic virus genotypes, comprised of previously-described viruses from Anatolia and the Balkans, with unique fingerprints in conserved amino acid motifs in viral replicase. A novel tick phlebovirus group was discovered circulating in the Balkans and Turkey, with at least three genotypes or species. No evidence for replication in vertebrates or infections in clinical cases could be demonstrated.
Topics: Animals; Chlorocebus aethiops; Genotype; Humans; Mice; Phlebovirus; Phylogeny; RNA-Dependent RNA Polymerase; Ticks; Turkey; Vero Cells; Viral Proteins
PubMed: 31374842
DOI: 10.3390/v11080703 -
The Journal of Veterinary Medical... Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a tick-borne virus called severe fever with thrombocytopenia syndrome virus...
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.
Topics: Animals; Humans; Cats; Mice; Dogs; Severe Fever with Thrombocytopenia Syndrome; Dependovirus; Phlebovirus; Bunyaviridae Infections; COVID-19 Vaccines; Cat Diseases; HEK293 Cells; Dog Diseases; Glycoproteins; Thrombocytopenia; Rodent Diseases
PubMed: 38143087
DOI: 10.1292/jvms.23-0375 -
Viruses Aug 2021Phleboviruses (genus , family ) are emerging pathogens of humans and animals. Sand-fly-transmitted phleboviruses are found in Europe, Africa, the Middle East, and the...
Phleboviruses (genus , family ) are emerging pathogens of humans and animals. Sand-fly-transmitted phleboviruses are found in Europe, Africa, the Middle East, and the Americas, and are responsible for febrile illness and nervous system infections in humans. Rio Grande virus (RGV) is the only reported phlebovirus in the United States. Isolated in Texas from southern plains woodrats, RGV is not known to be pathogenic to humans or domestic animals, but serologic evidence suggests that sheep () and horses () in this region have been infected. Rift Valley fever virus (RVFV), a phlebovirus of Africa, is an important pathogen of wild and domestic ruminants, and can also infect humans with the potential to cause severe disease. The introduction of RVFV into North America could greatly impact U.S. livestock and human health, and the development of vaccines and countermeasures is a focus of both the CDC and USDA. We investigated the potential for serologic reagents used in RVFV diagnostic assays to also detect cells infected with RGV. Western blots and immunocytochemistry assays were used to compare the antibody detection of RGV, RVFV, and two other New World phlebovirus, Punta Toro virus (South and Central America) and Anhanga virus (Brazil). Antigenic cross-reactions were found using published RVFV diagnostic reagents. These findings will help to inform test interpretation to avoid false positive RVFV diagnoses that could lead to public health concerns and economically costly agriculture regulatory responses, including quarantine and trade restrictions.
Topics: Animals; Bunyaviridae Infections; Cross Reactions; Horses; Phlebovirus; Reagent Kits, Diagnostic; Rift Valley Fever; Rift Valley fever virus; Serologic Tests; Sheep; United States
PubMed: 34578299
DOI: 10.3390/v13091719 -
Emerging Infectious Diseases Dec 2016Heartland virus (HRTV) is a recently described phlebovirus initially isolated in 2009 from 2 humans who had leukopenia and thrombocytopenia. Serologic assessment of...
Heartland virus (HRTV) is a recently described phlebovirus initially isolated in 2009 from 2 humans who had leukopenia and thrombocytopenia. Serologic assessment of domestic and wild animal populations near the residence of 1 of these persons showed high exposure rates to raccoons, white-tailed deer, and horses. To our knowledge, no laboratory-based assessments of viremic potential of animals infected with HRTV have been performed. We experimentally inoculated several vertebrates (raccoons, goats, chickens, rabbits, hamsters, C57BL/6 mice, and interferon-α/β/γ receptor-deficient [Ag129]) mice with this virus. All animals showed immune responses against HRTV after primary or secondary exposure. However, neutralizing antibody responses were limited. Only Ag129 mice showed detectable viremia and associated illness and death, which were dose dependent. Ag129 mice also showed development of mean peak viral antibody titers >8 log PFU/mL, hemorrhagic hepatic lesions, splenomegaly, and large amounts of HRTV antigen in mononuclear cells and hematopoietic cells in the spleen.
Topics: Animal Diseases; Animals; Antibodies, Neutralizing; Antibodies, Viral; Biopsy; Bunyaviridae Infections; Cricetinae; Disease Models, Animal; Disease Susceptibility; Female; Host-Pathogen Interactions; Male; Mice; Mice, Knockout; Mortality; Phlebovirus; Rabbits; Raccoons; Receptors, Interferon; Serologic Tests; Vertebrates; Viremia
PubMed: 27869591
DOI: 10.3201/eid2212.160472 -
The Journal of Infectious Diseases Dec 2023Severe fever with thrombocytopenia syndrome (SFTS) virus was first isolated in China in 2009 and has since spread to several Asian countries. SFTS is closely related to... (Observational Study)
Observational Study
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) virus was first isolated in China in 2009 and has since spread to several Asian countries. SFTS is closely related to environmental factors that accelerate vector growth. We evaluated the associations of SFTS and deforestation with environmental variables.
METHODS
For this observational study, we generated multiple Poisson models using national SFTS outbreak data (2013-2018) and official environmental data for Korea. We included established risk factors as variables. Deforestation was used as the main variable. All variables were analyzed according to their spatial characteristics using the R-INLA package.
RESULTS
SFTS cases increased over time and peaked in 2017, at 272, followed by a decrease in 2018. Disease mapping showed a high incidence of SFTS nationwide, with particular risks in Gangwon and Gyeonggi Provinces in the north, and Jeju in the south of South Korea. Deforestation was significantly associated with a higher risk of SFTS in the final model (relative risk, 1.751 [95% confidence interval, 1.125-2.743]).
CONCLUSIONS
SFTS outbreaks are associated with deforestation. Therefore, deforestation in Gyeonggi, Gangwon, and Jeju provinces of South Korea needs to be considered in vector-control strategies and active surveillance of SFTS occurrence.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; Conservation of Natural Resources; Phlebovirus; China
PubMed: 37265042
DOI: 10.1093/infdis/jiad196 -
Microbes and Infection Feb 2015Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia with case fatality up to 50%. SFTS is caused by SFTSV, a tick borne... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia with case fatality up to 50%. SFTS is caused by SFTSV, a tick borne bunyavirus. In endemic area in China 1%-3% population was infected with SFTSV, but age is critical risk factor for hospitalization and death of SFTS patients.
Topics: Animals; Arthropod Vectors; Bunyaviridae Infections; China; Disease Models, Animal; Hemorrhagic Fevers, Viral; Humans; Phlebovirus; Syndrome; Thrombocytopenia; Virus Replication
PubMed: 25498868
DOI: 10.1016/j.micinf.2014.12.002