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Frontiers in Immunology 2024Dabie Banda virus (DBV), a tick-borne pathogen, was first identified in China in 2009 and causes profound symptoms including fever, leukopenia, thrombocytopenia and... (Review)
Review
Dabie Banda virus (DBV), a tick-borne pathogen, was first identified in China in 2009 and causes profound symptoms including fever, leukopenia, thrombocytopenia and multi-organ dysfunction, which is known as severe fever with thrombocytopenia syndrome (SFTS). In the last decade, global incidence and mortality of SFTS increased significantly, especially in East Asia. Though previous studies provide understandings of clinical and immunological characteristics of SFTS development, comprehensive insight of antiviral immunity response is still lacking. Here, we intensively discuss the antiviral immune response after DBV infection by integrating previous ex- and in-vivo studies, including innate and adaptive immune responses, anti-viral immune responses and long-term immune characters. A comprehensive overview of potential immune targets for clinical trials is provided as well. However, development of novel strategies for improving the prognosis of the disease remains on challenge. The current review may shed light on the establishment of immunological interventions for the critical disease SFTS.
Topics: Animals; Humans; Adaptive Immunity; Immunity, Innate; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome
PubMed: 38646523
DOI: 10.3389/fimmu.2024.1348836 -
Journal of Medical Entomology Nov 2023Heartland (HRTV) and Bourbon (BRBV) viruses are newly identified tick-borne viruses, isolated from serious clinical cases in 2009 and 2014, respectively. Both viruses... (Review)
Review
Heartland (HRTV) and Bourbon (BRBV) viruses are newly identified tick-borne viruses, isolated from serious clinical cases in 2009 and 2014, respectively. Both viruses originated in the lower Midwest United States near the border of Missouri and Kansas, cause similar disease manifestations, and are presumably vectored by the same tick species, Amblyomma americanum Linnaeus (Ixodida: Ixodidae). In this article, we provide a current review of HRTV and BRBV, including the virology, epidemiology, and ecology of the viruses with an emphasis on the tick vector. We touch on current challenges of vector control and surveillance, and we discuss future directions in the study of these emergent pathogens.
Topics: United States; Animals; Ixodidae; Ticks; Amblyomma; Phlebovirus; Missouri
PubMed: 37862097
DOI: 10.1093/jme/tjad060 -
Current Opinion in Insect Science Aug 2017Old World sandfly-borne phleboviruses are classified into three serological complexes: Sandfly fever Sicilian, Sandfly fever Naples and Salehabad. Human pathogens... (Review)
Review
Old World sandfly-borne phleboviruses are classified into three serological complexes: Sandfly fever Sicilian, Sandfly fever Naples and Salehabad. Human pathogens (febrile illness ['sandfly fever'], neuroinvasive infections) belong to the two first complexes. The increasing number of newly discovered sandfly-borne phleboviruses raises concerns about their medical and veterinary importance. They occupy a wide geographic area from Mediterranean basin to North Africa and the Middle East to the central Asia. At least nine species of sandflies can transmit these viruses. Recent results suggest that sandfly vectors are not as specific for viruses as initially believed. Recent seroprevalence studies demonstrate that humans and domestic animals are heavily exposed. Specific molecular diagnostic methods must be developed and implemented in clinical microbiology laboratories.
Topics: Animals; Animals, Domestic; Humans; Insect Vectors; Phlebotomus Fever; Phlebovirus; Psychodidae; Seroepidemiologic Studies
PubMed: 28805633
DOI: 10.1016/j.cois.2017.05.019 -
Journal of Virological Methods Jun 2016This study reports the pan-phlebovirus assay capable of detecting both sandfly/mosquito- and tick-borne phleboviruses. Sensitivity and specificity of the assay was...
This study reports the pan-phlebovirus assay capable of detecting both sandfly/mosquito- and tick-borne phleboviruses. Sensitivity and specificity of the assay was verified using a panel of arboviruses. The RT-PCR assay is simple and sensitive, and thus well suited for screening of field samples.
Topics: Bunyaviridae Infections; Humans; Molecular Diagnostic Techniques; Phlebovirus; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Virology
PubMed: 26947398
DOI: 10.1016/j.jviromet.2016.02.009 -
The American Journal of Tropical... Feb 2020The genus is a diverse group of globally occurring viruses, including tick-, mosquito-, and sand fly-borne pathogens. Phleboviruses have historically been classified by...
The genus is a diverse group of globally occurring viruses, including tick-, mosquito-, and sand fly-borne pathogens. Phleboviruses have historically been classified by serological methods. However, molecular methods alone have been used to identify emergent novel and related strains in recent years. This makes reconciling the classification of historically and newly characterized viruses challenging. To address this in part, we describe the characterization of the genomes of the Frijoles and Chilibre species complex phleboviruses, and three unclassified phleboviruses isolated in the Americas: Caimito, Itaporanga, and Rio Grande viruses that had previously only been described at the serological level. With the exception of , the phleboviruses sequenced in this study are phylogenetically related to the current species , , or the Chagres antigenic complex. Unexpectedly, molecular and phylogenetic analysis suggests Chilibre and Caimito viruses are taxonomically related to the family . These viruses have a genomic architecture similar to peribunyaviruses and form monophyletic groups within the genus . Our data highlight the importance of reconciling serological and molecular taxonomic classification. In addition, we suggest the taxonomy of Chilibre and Caimito viruses should be revised.
Topics: Americas; Animals; Genome, Viral; Humans; Phlebovirus; Phylogeny
PubMed: 31802735
DOI: 10.4269/ajtmh.19-0717 -
Frontiers in Immunology 2021The genus consists of seven tick-borne bunyaviruses, among which four are known to infect humans. , severe fever with thrombocytopenia syndrome virus (SFTSV), poses... (Review)
Review
The genus consists of seven tick-borne bunyaviruses, among which four are known to infect humans. , severe fever with thrombocytopenia syndrome virus (SFTSV), poses serious threats to public health worldwide. SFTSV is a tick-borne virus mainly reported in China, South Korea, and Japan with a mortality rate of up to 30%. To date, most immunology-related studies focused on the antagonistic role of SFTSV non-structural protein (NSs) in sequestering RIG-I-like-receptors (RLRs)-mediated type I interferon (IFN) induction and type I IFN mediated signaling pathway. It is still elusive whether the interaction of SFTSV and other conserved innate immune responses exists. As of now, no specific vaccines or therapeutics are approved for SFTSV prevention or treatments respectively, in part due to a lack of comprehensive understanding of the molecular interactions occurring between SFTSV and hosts. Hence, it is necessary to fully understand the host-virus interactions including antiviral responses and viral evasion mechanisms. In this review, we highlight the recent progress in understanding the pathogenesis of SFTS and speculate underlying novel mechanisms in response to SFTSV infection.
Topics: Asia, Southeastern; Autophagy; DEAD Box Protein 58; Asia, Eastern; Humans; Immune Evasion; Immunity, Innate; Interferon Type I; Pakistan; Phlebovirus; Pyroptosis; Receptors, Immunologic; Severe Fever with Thrombocytopenia Syndrome; Signal Transduction; Viral Nonstructural Proteins; Virus Replication
PubMed: 34122440
DOI: 10.3389/fimmu.2021.676861 -
EBioMedicine Jan 2024Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that causes severe hemorrhagic fever in humans, but no FDA-approved specific...
BACKGROUND
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen that causes severe hemorrhagic fever in humans, but no FDA-approved specific antivirals or vaccines are available to treat or prevent SFTS.
METHODS
The plasmids construction and transfection were performed to generate the recombinant SFTSV harboring the nanoluciferase gene (SFTSV-Nluc). Immunostaining plaque assay was performed to measure viral titers, and DNA electrophoresis and Sanger sequencing were performed to evaluate the genetic stability. Luciferase assay and quantitative RT-PCR were performed to evaluate the efficacy of antivirals in vitro. Bioluminescence imaging, titration of virus from excised organs, hematology, and histopathology and immunohistochemistry were performed to evaluate the efficacy of antivirals in vivo.
FINDINGS
SFTSV-Nluc exhibited high genetic stability and replication kinetics similar to those of wild-type virus (SFTSVwt), then a rapid high-throughput screening system for identifying inhibitors to treat SFTS was developed, and a nucleoside analog, 4-FlU, was identified to effectively inhibit SFTSV in vitro. SFTSV-Nluc mimicked the replication characteristics and localization of SFTSVwt in counterpart model mice. Bioluminescence imaging of SFTSV-Nluc allowed real-time visualization and quantification of SFTSV replication in the mice. 4-FlU was demonstrated to inhibit the replication of SFTSV with more efficiency than T-705 and without obvious adverse effect in vivo.
INTERPRETATION
The high-throughput screening system based on SFTSV-Nluc for use in vitro and in vivo revealed that a safe and effective antiviral nucleoside analog, 4-FlU, may be a basis for the strategic treatment of SFTSV and other bunyavirus infections, paving the way for the discovery of antivirals.
FUNDING
This work was supported by grants from the National Key Research and Development Plan of China (2021YFC2300700 to L. Zhang, 2022YFC2303300 to L. Zhang), Strategic Priority Research Program of Chinese Academy of Sciences (XDB0490000 to L. Zhang), National Natural Science Foundation of China (31970165 to L. Zhang, U22A20379 to G. Xiao), the Science and Technology Commission of Shanghai Municipality (21S11903100 to Y. Xie), Hubei Natural Science Foundation for Distinguished Young Scholars (2022CFA099 to L. Zhang).
Topics: Humans; Animals; Mice; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Nucleosides; China; Antiviral Agents; Fever
PubMed: 38176215
DOI: 10.1016/j.ebiom.2023.104944 -
EMBO Molecular Medicine Mar 2024Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening disease caused by a novel bunyavirus (SFTSV), mainly transmitted by ticks. With no effective...
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.
Topics: Animals; Humans; Mice; Bunyaviridae Infections; Phlebovirus; B7-H1 Antigen; Severe Fever with Thrombocytopenia Syndrome; Leukocytes, Mononuclear; Programmed Cell Death 1 Receptor
PubMed: 38366162
DOI: 10.1038/s44321-024-00026-0 -
The Journal of Veterinary Medical... Jul 2022The present study investigated severe fever with thrombocytopenia syndrome virus (SFTSV) infection in raccoons in Wakayama Prefecture from 2007 to 2019. To perform...
The present study investigated severe fever with thrombocytopenia syndrome virus (SFTSV) infection in raccoons in Wakayama Prefecture from 2007 to 2019. To perform surveillance, an enzyme-linked immunosorbent assay (ELISA) was established, and the sensitivity and specificity of the ELISA were 100% in comparison with a 50% focus-reduction neutralization assay. Using the established ELISA, we performed serosurveillance of SFTSV infection in 2,299 raccoons in Tanabe region, Wakayama Prefecture from 2007 to 2019. The first anti-SFTSV-positive raccoon was captured in October 2009. The seroprevalence of SFTSV infection was <10% between April 2009 and March 2013, 23.9% between April 2013 and March 2014, 37.5% between April, 2014 and March 2015, and over 50% from April 2015. Next, we performed detection of SFTSV genes in sera of raccoons captured in Wakayama Prefecture after April 2013. The results indicated that 2.4% of raccoons were positive for SFTSV genes and that the frequency of SFTSV infection among raccoons between January and March (0.7%) was lower than that between April and June (3.4%). In addition, virus genes were detected from many specimens, including sera and feces of two raccoons, and viral antigens were detected in lymphoid cells in lymphoid follicles in the colon by immunohistochemical staining. In conclusion, SFTSV had recently invaded the area and had rapidly spread among wild animals. The first patient in this area was reported in June 2014, indicating that raccoons are good sentinels for assessing the risk of SFTSV in humans.
Topics: Animals; Antibodies, Viral; Bunyaviridae Infections; Phlebovirus; Raccoons; Seroepidemiologic Studies; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35650167
DOI: 10.1292/jvms.22-0236 -
PLoS Neglected Tropical Diseases Aug 2022SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents...
SFTSV, a tick-borne bunyavirus causing a severe hemorrhagic fever termed as severe fever with thrombocytopenia syndrome (SFTS). To evaluate the potential role of rodents and its ectoparasitic chiggers in the transmission of SFTSV, we collected wild rodents and chiggers on their bodies from a rural area in Qingdao City, Shandong Province, China in September 2020. PCR amplification of the M and L segments of SFTSV showed that 32.3% (10/31) of rodents and 0.2% (1/564) of chiggers (Leptotrombidium deliense) from the rodents were positive to SFTSV. Our results suggested that rodents and chiggers may play an important role in the transmission of SFTSV, although the efficiency of chiggers to transmit SFTSV needs to be further investigated experimentally.
Topics: Animals; Bunyaviridae Infections; China; Fever; Mite Infestations; Phlebovirus; Rodentia; Ticks; Trombiculidae
PubMed: 36037170
DOI: 10.1371/journal.pntd.0010698