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Viruses Jun 2016The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. Most prominent members... (Review)
Review
The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. Most prominent members include Rift Valley fever virus (RVFV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), Toscana virus (TOSV), Punta Toro virus (PTV), and the two new members severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV). The nonstructural protein NSs is well established as the main phleboviral virulence factor in the mammalian host. NSs acts as antagonist of the antiviral type I interferon (IFN) system. Recent progress in the elucidation of the molecular functions of a growing list of NSs proteins highlights the astonishing variety of strategies employed by phleboviruses to evade the IFN system.
Topics: Animals; Antiviral Agents; Host-Pathogen Interactions; Humans; Immune Evasion; Interferon Type I; Phlebovirus; Viral Nonstructural Proteins
PubMed: 27338447
DOI: 10.3390/v8060174 -
PLoS Pathogens Mar 2023Toscana virus (TOSV) (Bunyavirales, Phenuiviridae, Phlebovirus, Toscana phlebovirus) and other related human pathogenic arboviruses are transmitted by phlebotomine sand...
Toscana virus (TOSV) (Bunyavirales, Phenuiviridae, Phlebovirus, Toscana phlebovirus) and other related human pathogenic arboviruses are transmitted by phlebotomine sand flies. TOSV has been reported in nations bordering the Mediterranean Sea among other regions. Infection can result in febrile illness as well as meningitis and encephalitis. Understanding vector-arbovirus interactions is crucial to improving our knowledge of how arboviruses spread, and in this context, immune responses that control viral replication play a significant role. Extensive research has been conducted on mosquito vector immunity against arboviruses, with RNA interference (RNAi) and specifically the exogenous siRNA (exo-siRNA) pathway playing a critical role. However, the antiviral immunity of phlebotomine sand flies is less well understood. Here we were able to show that the exo-siRNA pathway is active in a Phlebotomus papatasi-derived cell line. Following TOSV infection, distinctive 21 nucleotide virus-derived small interfering RNAs (vsiRNAs) were detected. We also identified the exo-siRNA effector Ago2 in this cell line, and silencing its expression rendered the exo-siRNA pathway largely inactive. Thus, our data show that this pathway is active as an antiviral response against a sand fly transmitted bunyavirus, TOSV.
Topics: Animals; Humans; Sandfly fever Naples virus; Phlebotomus; Psychodidae; RNA Interference; Phlebovirus; Arboviruses; RNA, Small Interfering
PubMed: 36996243
DOI: 10.1371/journal.ppat.1011283 -
Frontiers in Cellular and Infection... 2022Severe fever with thrombocytopenia syndrome (SFTS) is an emerging arboviral infectious disease with a high rate of lethality in susceptible humans and caused by severe... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging arboviral infectious disease with a high rate of lethality in susceptible humans and caused by severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). Currently, neither vaccine nor specific antiviral drugs are available. In recent years, given the fact that both the number of SFTS cases and epidemic regions are increasing year by year, SFTS has become a public health problem. SFTSV can be internalized into host cells through the interaction between SFTSV glycoproteins and cell receptors and can activate the host immune system to trigger antiviral immune response. However, SFTSV has evolved multiple strategies to manipulate host factors to create an optimal environment for itself. Not to be discounted, host genetic factors may be operative also in the never-ending winning or losing wars. Therefore, the identifications of SFTSV, host immune and genetic factors, and their interactions are critical for understanding the pathogenic mechanisms of SFTSV infection. This review summarizes the updated pathogenesis of SFTS with regard to virus, host immune response, and host genetic factors to provide some novel perspectives of the prevention, treatment, as well as drug and vaccine developments.
Topics: Antiviral Agents; Bunyaviridae Infections; Communicable Diseases, Emerging; Glycoproteins; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35782112
DOI: 10.3389/fcimb.2022.808098 -
PLoS Neglected Tropical Diseases Sep 2023Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The...
Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The clinical disease characteristics and case fatality rates of SFTSV may vary across distinct regions and among different variant genotypes. From 2018 to 2022, we surveyed and recruited 202 severe fever with thrombocytopenia syndrome (SFTS) patients in Hubei Province, a high-incidence area of the epidemic, and conducted timely and systematic research on the disease characteristics, SFTSV diversity, and the correlation between virus genome variation and clinical diseases. Our study identified at least 6 genotypes of SFTSV prevalent in Hubei Province based on the analysis of the S, M, and L genome sequences of 88 virus strains. Strikingly, the dominant genotype of SFTSV was found to change during the years, indicating a dynamic shift in viral genetic diversity in the region. Phylogenetic analysis revealed the genetic exchange of Hubei SFTSV strains was relatively frequent, including 3 reassortment strains and 8 recombination strains. Despite the limited sample size, SFTSV C1 genotype may be associated with higher mortality compared to the other four genotypes, and the serum amyloid A (SAA) level, an inflammatory biomarker, was significantly elevated in these patients. Overall, our data summarize the disease characteristics of SFTSV in Hubei Province, highlight the profound changes in viral genetic diversity, and indicate the need for in-depth monitoring and exploration of the relationship between viral mutations and disease severity.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; Phylogeny; Phlebovirus; China; Genetic Variation
PubMed: 37721962
DOI: 10.1371/journal.pntd.0011654 -
Viruses Jul 2021In the last two decades, molecular surveys of arboviruses have enabled the identification of several new viruses, contributing to the knowledge of viral diversity and...
In the last two decades, molecular surveys of arboviruses have enabled the identification of several new viruses, contributing to the knowledge of viral diversity and providing important epidemiological data regarding possible new emerging viruses. A combination of diagnostic assays, Illumina sequencing and phylogenetic inference are here used to characterize two new strains isolated from sandflies collected in the Arrábida region, Portugal. Whole genome sequence analysis enabled their identification as reassortants and the recognition of genomic variants co-circulating in Portugal. Much is still unknown about the life cycle, geographic range, evolutionary forces and public health importance of these viruses in Portugal and elsewhere, and more studies are needed.
Topics: Animals; Female; Genome, Viral; High-Throughput Nucleotide Sequencing; Phlebovirus; Phylogeny; Portugal; Psychodidae; RNA, Viral; Whole Genome Sequencing
PubMed: 34372617
DOI: 10.3390/v13071412 -
Parasites & Vectors Dec 2014Phlebotomine sandflies are vectors of several pathogens with significant impact for public health. This study was conducted to investigate and characterize phlebovirus...
BACKGROUND
Phlebotomine sandflies are vectors of several pathogens with significant impact for public health. This study was conducted to investigate and characterize phlebovirus and Leishmania infections in vector sandflies collected in the eastern Thrace region in Turkey and Northern Cyprus, where previous data indicate activity of these agents.
METHODS
Field sampling of sandflies was performed at 4 locations in Edirne and Tekirdag provinces of eastern Thrace and at 17 locations in Lefkosa, Girne, Magosa and Guzelyurt provinces of northern Cyprus. In sandfly pools, phlebovirus RNA and Leishmania DNA were screened via a generic polymerase chain reaction (PCR) and kinetoplast minicircle PCR, respectively. Selected sandfly specimens unsuitable for pathogen detection were identified to species level. Cytochrome oxidase 1 gene region was used for DNA barcoding of selected specimens and pathogen positive pools. Positive amplicons were cloned and characterized by sequencing.
RESULTS
A total of 2690 sandflies, collected from Eastern Thrace (15.4%) and Northern Cyprus (84.6%) were evaluated. Morphological examination of 780 specimens from Cyprus exhibited Phlebotomus perfiliewi sensu lato (72.6%), Phlebotomus tobbi (19.7%), Phlebotomus papatasi (2.8%), Laroussius sp. (1.6%) and Sergentomyia azizi (1.6%), Sergentomyia sp. (0.9%), Sergentomyia minuta (0.5%) and Phleobotomus jacusieli (0.1%) species. Pathogen screening was performed in 1910 specimens distributed in 195 pools. In eight pools of P.tobbi sandflies collected in Cyprus, Leishmania infantum DNA was demonstrated. Toscana virus (TOSV) genotype A sequences were identified in two pools of P. perfiliewi s.l. and one pool of P.tobbi sandflies from Cyprus. Co-infection of TOSV and Leishmania infantum was characterized in a P.tobbi pool. Sequences belonging to novel phleboviruses are revealed in three P. perfiliewi s.l. pools. One sequence, provisionally named Edirne virus, identified in Edirne province in eastern Thrace, demonstrated the highest rate of genomic similarity to Adria and Salehabad viruses. Furthermore, Girne 1 and Girne 2 viruses, identified in Girne province, revealed similarities to TOSV and Sandfly Fever Sicilian virus and related strains, respectively.
CONCLUSIONS
Activity of TOSV genotype A strains in Cyprus and co-infection of sandfly vectors with L. infantum was documented for the first time. Novel phlebovirus strains of unknown medical significance was identified in sampling regions.
Topics: Animals; Cyprus; Insect Vectors; Leishmania; Molecular Sequence Data; Phlebotomus; Phlebovirus; Phylogeny; Turkey
PubMed: 25499083
DOI: 10.1186/s13071-014-0575-6 -
International Journal of Infectious... Sep 2023Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal...
OBJECTIVES
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal dynamics of the SFTSV-specific neutralizing antibody (NAb) and the related factors in patients with SFTS.
METHODS
A prospective cohort study of patients with laboratory-confirmed SFTS were conducted. Antiglomerulonephritis-immunoglobulin G (anti-Gn-IgG) and NAb titers were examined in serially collected serum samples, and their dynamic features were analyzed.
RESULTS
NAb was initially detected at 15 days after symptom onset in surviving patients with SFTS, with positive rates of 37.21% (16/43), whereas neither anti-Gn-IgG antibody nor NAb was detected in patients with fatal SFTS during their hospitalization. The NAb levels reached the peak at 2 months after symptom onset, and then gradually declined, with a rapid downward trend from 6 months to 4 years and a relatively slow downward trend from 5 to 10 years. There was a positive correlation between NAb and anti-Gn-IgG titers in surviving patients with SFTS (r = 0.699, P <0.001). Patients with a mild illness or low viral load experienced early NAb seroconversion. Six different dynamic patterns of NAb were noted in surviving patients.
CONCLUSION
These data provide useful information regarding the dynamic changes in NAb in patients with SFTS during the acute and convalescent phases and the follow-up period.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Antibodies, Neutralizing; Prospective Studies; Bunyaviridae Infections; Antibodies, Viral; Phlebovirus; Immunoglobulin G
PubMed: 37247691
DOI: 10.1016/j.ijid.2023.05.018 -
Journal of Virology Jul 2022In this issue, Gao and colleagues (J Virol 96:e00167-22, https://doi.org/10.1128/JVI.00167-22) dissect innate immune signaling in a microglial cell line infected with...
In this issue, Gao and colleagues (J Virol 96:e00167-22, https://doi.org/10.1128/JVI.00167-22) dissect innate immune signaling in a microglial cell line infected with severe fever with thrombocytopenia syndrome virus (SFTSV). This virus has been designated a priority pathogen by the World Health Organization due to its capacity to induce a fatal cytokine storm. The study's findings attribute the pathogenesis to induction of the host inflammasome response by the SFTSV nonstructural protein.
Topics: Bunyaviridae Infections; Encephalitis; Humans; Phlebovirus; Signal Transduction; Viral Nonstructural Proteins
PubMed: 35695504
DOI: 10.1128/jvi.00454-22 -
Frontiers in Cellular and Infection... 2023The study aimed to comprehensively describe and evaluate the pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients with...
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 , were observed in 22 cases. Bacterial infections, with and carbapenem-resistant as the main pathogens, were identified in 20 cases. SFTS patients with co-infection exhibited higher mortality (=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.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Coinfection; Retrospective Studies; Phlebovirus; Bunyaviridae Infections; Thrombocytopenia
PubMed: 38106473
DOI: 10.3389/fcimb.2023.1298050 -
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