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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 -
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 -
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 -
Scientific Reports Mar 2018Autophagy is essential for eukaryotic cell homeostasis and can perform both anti-viral and pro-viral roles depending on the kinds of viruses, cell types and cell...
Autophagy is essential for eukaryotic cell homeostasis and can perform both anti-viral and pro-viral roles depending on the kinds of viruses, cell types and cell environment. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a newly discovered tick-borne virus in the Phenuiviridae family that causes a severe hemorrhagic fever disease in East Asia. In this study we determined interactions between SFTSV and autophagy. Our results showed that LC3-II (microtubule associated protein 1 light chain 3-II) protein accumulated from 4 h to 24 h after SFTSV infection compared to mock-infected Vero cells, and the use of E64d and pepstatin A did not affect the expression of LC3-II protein, which indicated that the increased LC3-II may be the result of inhibition of autophagic degradation caused by SFTSV infection. However, knockdown of LC3B promotes SFTSV replication, which indicated a negative role of LC3B protein in SFTSV replication. We also detected co-localization of SFTSV non-structure (NSs) protein with LC3B, p62 and Lamp2b respectively in SFTSV infected Vero cells, which indicated the possibility of selective autophagy or chaperone-mediated autophagy involving in SFTSV infection. Our results indicated that SFTSV infection promotes LC3 accumulation and several proteins of the autophagy pathway co-localize with NSs protein during SFTSV infection.
Topics: Animals; Autophagy; Chlorocebus aethiops; Host-Pathogen Interactions; Humans; Mice, Inbred BALB C; Microtubule-Associated Proteins; Phlebotomus Fever; Phlebovirus; Vero Cells; Viral Nonstructural Proteins; Virus Replication
PubMed: 29588492
DOI: 10.1038/s41598-018-23610-0 -
Viruses Sep 2022Viral coinfections can modulate the severity of parasitic diseases, such as human cutaneous leishmaniasis. Leishmania parasites infect thousands of people worldwide and...
Viral coinfections can modulate the severity of parasitic diseases, such as human cutaneous leishmaniasis. Leishmania parasites infect thousands of people worldwide and cause from single cutaneous self-healing lesions to massive mucosal destructive lesions. The transmission to vertebrates requires the bite of Phlebotomine sandflies, which can also transmit Phlebovirus. We have demonstrated that Leishmania infection requires and triggers the Endoplasmic stress (ER stress) response in infected macrophages. In the present paper, we tested the hypothesis that ER stress is increased and required for the aggravation of infection due to coinfection with . We demonstrated that Icoaraci induces the ER stress program in macrophages mediated by the branches IRE/XBP1 and PERK/ATF4. The coinfection with potentiates and sustains the ER stress, and the inhibition of IRE1α or PERK results in poor viral replication and decreased parasite load in macrophages. Importantly, we observed an increase in viral replication during the coinfection with . Our results demonstrated the role of ER stress branches IRE1/XBP1 and PERK/ATF4 in the synergic effect on the Leishmania increased load during coinfection and suggests that infection can also increase the replication of in macrophages.
Topics: Animals; Coinfection; Endoribonucleases; Humans; Leishmania; Leishmaniasis; Orthobunyavirus; Phlebovirus; Protein Serine-Threonine Kinases
PubMed: 36146755
DOI: 10.3390/v14091948 -
Viruses Apr 2021Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present,... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals.
Topics: Animals; Cat Diseases; Cats; Cricetinae; Disease Models, Animal; Dog Diseases; Dogs; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Phlebovirus; Primates; Severe Fever with Thrombocytopenia Syndrome; Viral Vaccines
PubMed: 33917632
DOI: 10.3390/v13040627 -
Viruses Sep 2018First identified in two Missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to severe... (Review)
Review
First identified in two Missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne phlebovirus producing similar symptoms in China, Korea, and Japan. Field isolations of HRTV from several life stages of unfed, host-seeking , the lone star tick, implicated it as a putative vector capable of transstadial transmission. Laboratory vector competence assessments confirmed transstadial transmission of HRTV, demonstrated vertical infection, and showed co-feeding infection between . A vertical infection rate of 33% from adult females to larvae in the laboratory was observed, while only one of 386 pools of molted nymphs (1930) reared from co-feeding larvae was positive for HRTV (maximum-likelihood estimate of infection rate = 0.52/1000). Over 35 human HRTV cases, all within the distribution range of , have been documented. Serological testing of wildlife in areas near the index human cases, as well as in widely separated regions of the eastern United States where occur, indicated many potential hosts such as raccoons and white-tailed deer. Attempts, however, to experimentally infect mice, rabbits, hamsters, chickens, raccoons, goats, and deer failed to produce detectable viremia. Immune-compromised mice and hamsters are the only susceptible models. Vertical infection augmented by co-feeding transmission could play a role in maintaining the virus in nature. A more complete assessment of the natural transmission cycle of HRTV coupled with serosurveys and enhanced HRTV disease surveillance are needed to better understand transmission dynamics and human health risks.
Topics: Animals; Bunyaviridae Infections; Disease Management; Disease Models, Animal; Disease Vectors; Host-Pathogen Interactions; Humans; Phlebovirus; Phylogeny; Population Surveillance; United States
PubMed: 30223439
DOI: 10.3390/v10090498