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Viruses Nov 2023Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans....
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection caused by the SFTS virus (SFTSV), with a high fatality rate of approximately 30% in humans. In recent years, cases of contact infection with SFTSV via bodily fluids of infected dogs and cats have been reported. In this study, clinical and virological analyses were performed in two dogs in which SFTSV infection was confirmed for the first time in the Toyama prefecture. Both dogs recovered; however, one was severely ill and the other mildly ill. The amount of the SFTSV gene was reduced to almost similar levels in both dogs. In the dogs' sera, the SFTSV gene was detected at a low level but fell below the detection limit approximately 2 weeks after onset. Notably, the SFTSV gene was detected at levels several thousand times higher in urine than in other specimens from both dogs. Furthermore, the gene was detected in the urine for a long period of >2 months. The clinical signs disappeared on days 1 or 6 after onset, but infectious SFTSV was detected in the urine up to 3 weeks later. Therefore, it is necessary to be careful about contact with bodily fluids, especially urine, even after symptoms have disappeared.
Topics: Humans; Animals; Dogs; Cats; Severe Fever with Thrombocytopenia Syndrome; Cat Diseases; Bunyaviridae Infections; Dog Diseases; Phlebovirus
PubMed: 38005905
DOI: 10.3390/v15112228 -
Microorganisms Nov 2023Phleboviruses are classified into two main groups: the sandfly fever group (transmitted by sandflies and mosquitoes) and the Uukuniemi group (transmitted by ticks). Old...
Phleboviruses are classified into two main groups: the sandfly fever group (transmitted by sandflies and mosquitoes) and the Uukuniemi group (transmitted by ticks). Old World sandfly-borne viruses (SBVs) are classified into four main serocomplexes; sandfly fever Naples viruses (SFNVs), sandfly fever Sicilian viruses (SFSVs), Karimabad viruses (KARVs), and Salehabad viruses (SALVs). This study addresses current knowledge gaps on SBVs in Iran by focusing on identification and molecular epidemiology. We used PCR to examine DNA/RNA extracts to identify sandfly species and evaluate for SBV presence. We identified five specimens positive for phleboviruses: one for Tehran virus (TEHV), one for SFSV, and two and one for KARV. A phylogenetic tree indicated that the TEHV isolate from this study formed a cluster with previous isolates of TEHV, Zerdali virus, and Fermo virus. Meanwhile, the identified SFSV isolate fell in lineage I and was grouped with previous isolates of SFSVs and Dashli virus in Iran. Finally, the KARV isolates from this study formed a monophyletic clade in a sister relationship with other viruses in KARV lineages I and II. This comprehensive study on SBVs in Iran provided new insights into the molecular epidemiology of TEHV, SFSVs and KARVs in this country.
PubMed: 38004764
DOI: 10.3390/microorganisms11112754 -
One Health (Amsterdam, Netherlands) Dec 2023High seroprevalence rates of several phleboviruses have been reported in domestic animals and humans in sandfly-infested regions. Sandfly Fever Sicilian virus (SFSV) and...
High seroprevalence rates of several phleboviruses have been reported in domestic animals and humans in sandfly-infested regions. Sandfly Fever Sicilian virus (SFSV) and Toscana virus (TOSV) are two of these viruses commonly transmitted by sandflies. While SFSV can cause rapidly resolving mild febrile illness, TOSV could involve the central nervous system (CNS), causing diseases ranging from aseptic meningitis to meningoencephalitis. Sandfly-associated phleboviruses have not been investigated before in Saudi Arabia and are potential causes of infection given the prevalence of sandflies in the country. Here, we investigated the seroprevalence of SFSV and TOSV in the western region of Saudi Arabia in samples collected from blood donors, livestock animals, and animal handlers. An overall seroprevalence of 9.4% and 0.8% was found in humans for SFSV and TOSV, respectively. Seropositivity was significantly higher in non-Saudis compared to Saudis and increased significantly with age especially for SFSV. The highest seropositivity rate was among samples collected from animal handlers. Specifically, in blood donors, 6.4% and 0.7% tested positive for SFSV and TOSV nAbs, respectively. Animal handlers showed higher seroprevalence rates of 16% and 1% for anti-SFSV and anti-TOSV nAbs, respectively, suggesting that contact with livestock animals could be a risk factor. Indeed, sera from livestock animals showed seropositivity of 53.3% and 4.4% in cows, 27.5% and 7.8% in sheep, 2.2% and 0.0% in goats, and 10.0% and 2.3% in camels for SFSV and TOSV, respectively. Together, these results suggest that both SFSV and TOSV are circulating in the western region of Saudi Arabia in humans and livestock animals, albeit at different rates, and that age and contact with livestock animals could represent risk factors for infection with these viruses.
PubMed: 37520847
DOI: 10.1016/j.onehlt.2023.100601 -
Virologica Sinica Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. However, the...
Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. However, the viral-host interaction of SFTSV remains largely unknown. The heat-shock protein 90 (Hsp90) family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses. Here, we showed that Hsp90 is an important host factor involved in SFTSV infection. Hsp90 inhibitors significantly reduced SFTSV replication, viral protein expression, and the formation of inclusion bodies consisting of nonstructural proteins (NSs). Among viral proteins, NSs appeared to be the most reduced when Hsp90 inhibitors were used, and further analysis showed that their translation was affected. Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90 β specifically interacted with them. Knockdown of Hsp90 β expression also inhibited replication of SFTSV. These results suggest that Hsp90 β plays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus; Host Microbial Interactions; Bunyaviridae Infections
PubMed: 38008382
DOI: 10.1016/j.virs.2023.11.008 -
Scientific Reports Oct 2023Rift Valley fever (RVF) is a mosquito-borne zoonotic disease causing acute hemorrhagic fever. Accurate identification of mutations and phylogenetic characterization of...
Rift Valley fever (RVF) is a mosquito-borne zoonotic disease causing acute hemorrhagic fever. Accurate identification of mutations and phylogenetic characterization of RVF virus (RVFV) require whole-genome analysis. Universal primers to amplify the entire RVFV genome from clinical samples with low copy numbers are currently unavailable. Thus, we aimed to develop universal primers applicable for all known RVFV strains. Based on the genome sequences available from public databases, we designed eight pairs of universal PCR primers covering the entire RVFV genome. To evaluate primer universality, four RVFV strains (ZH548, Kenya 56 (IB8), BIME-01, and Lunyo), encompassing viral phylogenetic diversity, were chosen. The nucleic acids of the test strains were chemically synthesized or extracted via cell culture. These RNAs were evaluated using the PCR primers, resulting in successful amplification with expected sizes (0.8-1.7 kb). Sequencing confirmed that the products covered the entire genome of the RVFV strains tested. Primer specificity was confirmed via in silico comparison against all non-redundant nucleotide sequences using the BLASTn alignment tool in the NCBI database. To assess the clinical applicability of the primers, mock clinical specimens containing human and RVFV RNAs were prepared. The entire RVFV genome was successfully amplified and sequenced at a viral concentration of 10 copies/mL. Given the universality, specificity, and clinical applicability of the primers, we anticipate that the RVFV universal primer pairs and the developed method will aid in RVFV phylogenomics and mutation detection.
Topics: Animals; Humans; Rift Valley fever virus; Phylogeny; Rift Valley Fever; Hemorrhagic Fevers, Viral; Whole Genome Sequencing; RNA
PubMed: 37907670
DOI: 10.1038/s41598-023-45848-z -
Nucleic Acids Research Jun 2024Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that is now endemic to several East Asian countries. The viral large (L) protein catalyzes...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a human pathogen that is now endemic to several East Asian countries. The viral large (L) protein catalyzes viral transcription by stealing host mRNA caps via a process known as cap-snatching. Here, we establish an in vitro cap-snatching assay and present three high-quality electron cryo-microscopy (cryo-EM) structures of the SFTSV L protein in biologically relevant, transcription-specific states. In a priming-state structure, we show capped RNA bound to the L protein cap-binding domain (CBD). The L protein conformation in this priming structure is significantly different from published replication-state structures, in particular the N- and C-terminal domains. The capped-RNA is positioned in a way that it can feed directly into the RNA-dependent RNA polymerase (RdRp) ready for elongation. We also captured the L protein in an early-elongation state following primer-incorporation demonstrating that this priming conformation is retained at least in the very early stages of primer extension. This structural data is complemented by in vitro biochemical and cell-based assays. Together, these insights further our mechanistic understanding of how SFTSV and other bunyaviruses incorporate stolen host mRNA fragments into their viral transcripts thereby allowing the virus to hijack host cell translation machinery.
Topics: Humans; Cryoelectron Microscopy; Models, Molecular; Phlebovirus; Protein Conformation; RNA Caps; RNA, Viral; RNA-Dependent RNA Polymerase; Transcription, Genetic; Viral Proteins; Virus Replication; Host Microbial Interactions
PubMed: 38709882
DOI: 10.1093/nar/gkae330 -
Frontiers in Cellular and Infection... 2023Rift Valley fever virus (RVFV) is a (re)emerging mosquito-borne pathogen impacting human and animal health. How RVFV spreads through a population depends on...
Rift Valley fever virus (RVFV) is a (re)emerging mosquito-borne pathogen impacting human and animal health. How RVFV spreads through a population depends on population-level and individual-level interactions between vector, host and pathogen. Here, we estimated the probability for RVFV to transmit to naive animals by experimentally exposing lambs to a bite of an infectious mosquito, and assessed if and how RVFV infection subsequently developed in the exposed animal. mosquitoes, previously infected via feeding on a viremic lamb, were used to expose naive lambs to the virus. colony mosquitoes were used as they are easy to maintain and readily feed in captivity. Other mosquito spp. could be examined with similar methodology. Lambs were exposed to either 1-3 (low exposure) or 7-9 (high exposure) infectious mosquitoes. All lambs in the high exposure group became viremic and showed characteristic signs of Rift Valley fever within 2-4 days post exposure. In contrast, 3 out of 12 lambs in the low exposure group developed viremia and disease, with similar peak-levels of viremia as the high exposure group but with some heterogeneity in the onset of viremia. These results suggest that the likelihood for successful infection of a ruminant host is affected by the number of infectious mosquitoes biting, but also highlights that a single bite of an infectious mosquito can result in disease. The per bite mosquito-to-host transmission efficiency was estimated at 28% (95% confidence interval: 15 - 47%). We subsequently combined this transmission efficiency with estimates for life traits of or related mosquitoes into a Ross-McDonald mathematical model to illustrate scenarios under which major RVFV outbreaks could occur in naïve populations (i.e., R >1). The model revealed that relatively high vector-to-host ratios as well as mosquitoes feeding preferably on competent hosts are required for R to exceed 1. Altogether, this study highlights the importance of experiments that mimic natural exposure to RVFV. The experiments facilitate a better understanding of the natural progression of disease and a direct way to obtain epidemiological parameters for mathematical models.
Topics: Animals; Aedes; Mosquito Vectors; Rift Valley Fever; Rift Valley fever virus; Ruminants; Sheep; Viremia
PubMed: 38170150
DOI: 10.3389/fcimb.2023.1206089 -
Science Progress 2024The common gastrointestinal commensal is a mucin-degrading bacterium that is greatly reduced in individuals consuming a high-fat diet. Increasing evidence from a...
The common gastrointestinal commensal is a mucin-degrading bacterium that is greatly reduced in individuals consuming a high-fat diet. Increasing evidence from a variety of clinical and pre-clinical studies suggests that oral supplementation with can improve metabolic health and moderate systemic inflammation. We and others have demonstrated a role for administration in protection against infectious disease and the outcome from sepsis. Very recent studies have indicated the molecular mechanisms by which may interact with the host to influence systemic immune-regulation and control of microbial pathogenesis. Here we consider recent studies which demonstrate the efficacy of this potential next-generation probiotic in animal models of Typhimurium, and as well as influenza virus and phlebovirus. The potential mechanisms by which may influence local and systemic immune responses are discussed.
Topics: Animals; Humans; Verrucomicrobia; Akkermansia; Probiotics; Communicable Diseases
PubMed: 38490164
DOI: 10.1177/00368504241231159 -
Ticks and Tick-borne Diseases Jan 2024Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS...
Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerged tick-borne viral zoonosis and widely prevalent in China, Japan and South Korea. Most reported SFTS cases have been identified in mountainous and hilly areas, with a few in island areas. In this study, we conducted a systematic investigation about natural infection of SFTS virus (SFTSV) among humans, animals and ticks in a coastal endemic prefecture, containing island, plains and mountain settings, in Zhejiang Province, Southeastern China. From July 2020 to June 2021, 1117 participants completed a survey with questionnaire interview and serum testing. Meanwhile, 862 serum samples of domestic animals, 275 spleen tissue samples of wild animals and 829 ticks representing five species (predominantly Haemaphysalis longicornis and Rhipicephalus sanguineus sensu lato) were collected. The seroprevalence of anti-SFTSV total antibody and IgM antibody among the participants was 4.8 % (54/1117) and 0.6 % (7/1117), respectively. Multivariate logistic regression analysis indicated that living in the island area (OR=2.66; 95 %CI: 1.04-6.80; P = 0.041) was significantly associated with seropositivity of total antibody to SFTSV. Furthermore, a higher seroprevalence was observed in domestic animals (36.1 %), while the SFTSV-RNA infection rate was 0.4 % in wild animals and the minimum infection rate (MIR) was 0.8 % for all tick species combined. The only tick species infected with SFTSV was H. longicornis. The prevalence of SFTSV infection in the island area, manifested by anti-SFTSV total antibody (P = 0.012) and IgM antibody (P = 0.004) among humans, anti-SFTSV total antibody (P<0.001) among domestic animals, and SFTSV-RNA among ticks (P = 0.022), was significantly higher than that in the mountainous area and the plain area. Furthermore, phylogenetic analysis showed that SFTSV sequences obtained from ticks in the island area were clustered with reported strains in Japan and South Korea. These results suggest that islands in the study area might be an important natural focus of SFTSV.
Topics: Animals; Humans; Severe Fever with Thrombocytopenia Syndrome; Phylogeny; Seroepidemiologic Studies; Phlebovirus; Animals, Domestic; Animals, Wild; China; RNA; Rhipicephalus sanguineus; Immunoglobulin M; Bunyaviridae Infections
PubMed: 37981467
DOI: 10.1016/j.ttbdis.2023.102277 -
Emerging Infectious Diseases Sep 2023A new phlebovirus variant was isolated from an acute febrile patient in Chanchamayo, Peru. Genome characterization and p-distance analyses based on complete open reading...
A new phlebovirus variant was isolated from an acute febrile patient in Chanchamayo, Peru. Genome characterization and p-distance analyses based on complete open reading frames revealed that the virus is probably a natural reassortant of the Echarate virus (large and small segments) with a yet-unidentified phlebovirus (M segment).
Topics: Humans; Peru; Fever; Open Reading Frames; Phlebovirus
PubMed: 37610254
DOI: 10.3201/eid2909.230374