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PLoS Neglected Tropical Diseases Aug 2017Pathogens transmitted to humans by phlebotomine sand flies are neglected, as they cause infectious diseases that are not on the priority list of national and... (Review)
Review
Pathogens transmitted to humans by phlebotomine sand flies are neglected, as they cause infectious diseases that are not on the priority list of national and international public health systems. However, the infections caused by protozoa of the Leishmania genus and viruses belonging to the Phlebovirus genus (family Phenuiviridae)-the most significant group of viruses transmitted by sand flies-have a relevant role for human pathology. These infections are emerging in the Mediterranean region and will likely spread in forthcoming decades, posing a complex threat to human health. Four species and 2 hybrid strains of Leishmania are pathogenic for humans in the Mediterranean Basin, with an estimated annual incidence of 239,500-393,600 cases of cutaneous leishmaniasis and 1,200-2,000 cases of visceral leishmaniasis. Among the phleboviruses, Toscana virus can cause neuroinvasive infections, while other phleboviruses are responsible for a typical "3-day fever"; the actual incidence of Phlebovirus infections in the Mediterranean area is unknown, although at least 250 million people are exposed. Here, we reviewed the current literature on epidemiology of sand fly-borne infections in the Mediterranean Basin, with a focus on humans. Our analysis indicates the need for increased public health activities directed to determine the disease burden of these infections as well as to improve their surveillance. Among the emerging challenges concerning sand fly-borne pathogens, the relationships between sand fly-borne protozoa and viruses should be considered in future studies, including epidemiological links between Leishmania and phleboviruses as well as the conditional capacity for these pathogens to be involved in interactions that may evolve towards increased virulence.
Topics: Animals; Bunyaviridae Infections; Dogs; Humans; Insect Vectors; Leishmania; Leishmaniasis; Mediterranean Region; Phlebovirus; Psychodidae
PubMed: 28796786
DOI: 10.1371/journal.pntd.0005660 -
Uirusu 2015Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV), a novel phlebovirus reported to be... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus (SFTSV), a novel phlebovirus reported to be endemic to China in 2011. In Japan, the first SFTS patient was identified during the autumn of 2012; since then, over 100 SFTS patients have been reported. The SFTSV has been identified throughout Japan over the past two years; however, SFTS patients are specifically localized to western Japan. The clinical symptoms of SFTS include fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and various other symptoms, including muscular symptoms, neurological abnormalities, and coagulopathy. SFTS is often accompanied by hemophagocytic syndrome. The histopathological findings are characterized by necrotizing lymphadenitis, with infiltration of the virus-infected cells to the local lymph nodes. Pathophysiological analyses of SFTS include studies regarding the kinetics of cytokine production and immune responses in patients with SFTS and in SFTSV-infection animal models. This article aimed to survey the history of SFTS in Japan and to review the clinical, epidemiological, and virological aspects of SFTS and SFTSV infection.
Topics: Adult; Aged; Aged, 80 and over; Animals; Bunyaviridae Infections; Disease Models, Animal; Humans; Insect Vectors; Japan; Life Cycle Stages; Mice; Middle Aged; Phlebovirus; Severity of Illness Index; Ticks; Young Adult
PubMed: 26923953
DOI: 10.2222/jsv.65.7 -
The Journal of General Virology Nov 2021Sandfly-borne phleboviruses are distributed widely throughout the Mediterranean Basin, presenting a threat to public health in areas where they circulate. However, the...
Sandfly-borne phleboviruses are distributed widely throughout the Mediterranean Basin, presenting a threat to public health in areas where they circulate. However, the true diversity and distribution of pathogenic and apathogenic sandfly-borne phleboviruses remains a key issue to be studied. In the Balkans, most published data rely on serology-based studies although virus isolation has occasionally been reported. Here, we report the discovery of two novel sandfly-borne phleboviruses, provisionally named Zaba virus (ZABAV) and Bregalaka virus (BREV), which were isolated in Croatia and North Macedonia, respectively. This constitutes the first isolation of phleboviruses in both countries. Genetic analysis based on complete coding sequences indicated that ZABAV and BREV are distinct from each other and belong to the genus family . Phylogenetic and amino acid modelling of viral polymerase shows that ZABAV and BREV are new members of the species and the species, respectively. Moreover, sequence-based vector identification suggests that ZABAV is mainly transmitted by and BREV is mainly transmitted by . BREV neutralizing antibodies were detected in 3.3% of human sera with rates up to 16.7% in certain districts, demonstrating that BREV frequently infects humans in North Macedonia. viral growth kinetics experiments demonstrated viral replication of both viruses in mammalian and mosquito cells. experimental studies in mice suggest that ZABAV and BREV exhibit characteristics making them possible human pathogens.
Topics: Animals; Croatia; Insect Vectors; Mosquito Vectors; Phlebovirus; Phylogeny; Psychodidae; Republic of North Macedonia
PubMed: 34797756
DOI: 10.1099/jgv.0.001674 -
Nature Microbiology Mar 2019
Topics: Animals; Disease Models, Animal; Ferrets; Humans; Phlebovirus
PubMed: 30787477
DOI: 10.1038/s41564-019-0390-0 -
Microbiome Feb 2024Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps...
BACKGROUND
Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements.
RESULTS
We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated.
CONCLUSIONS
These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.
Topics: Animals; Humans; Ixodidae; Haemaphysalis longicornis; Virome; Phylogeny; Phlebovirus; Ticks
PubMed: 38378577
DOI: 10.1186/s40168-024-01753-9 -
Journal of Medical Virology Aug 2021Severe fever with thrombocytopenia syndrome (SFTS) is recognized as an emerging infectious disease. This study aimed to investigate the pathogenic mechanism of SFTS. A...
Severe fever with thrombocytopenia syndrome (SFTS) is recognized as an emerging infectious disease. This study aimed to investigate the pathogenic mechanism of SFTS. A total of 100 subjects were randomly included in the study. Cytokine levels were detected by enzyme-linked immunosorbent assay and the viral load was detected by micro drop digital PCR. The results showed that levels of interleukin-6 (IL-6), IL-8, IL-10, IFN-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), transforming growth factor-β1 (TGF-β1), and regulated upon activation normal T cell expressed and secreted factor (RANTES) differed significantly among the SFTS patient group, healthy people group, and asymptomatic infection group (p < .05). Compared to the healthy people group, the patient group had increased cytokine levels (IL-6, IL-10, IP-10, MCP-1, and IFN-γ) but reduced levels of IL-8, TGF-β1, and RANTES (p < .0167). IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1α, TGF-β1, and the RANTES levels had different trends after the onset of the disease. IL-6, IL-10, IP-10, and MCP-1 levels in severe patients were higher than those in mild patients (p < .05). There was a positive correlation between viral load and IL-6 and IP-10 but a negative correlation between viral load and RANTES. SFTSV could cause a cytokine change: the cytokine levels of patients had different degrees of fluctuation after the onset of the disease. The levels of IL-6 and IL-8 in the asymptomatic infection group were found between the SFTS patients group and the healthy people group. The levels of IL-6, IL-10, IP-10, and MCP-1 in the serum could reflect the severity of the disease, and the levels of IL-6, IP-10, and RANTES were correlated with the viral load.
Topics: Aged; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Severity of Illness Index; Viral Load
PubMed: 33590892
DOI: 10.1002/jmv.26877 -
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 -
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 -
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