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Journal of Microbiology (Seoul, Korea) Apr 2024Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually...
Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs.
Topics: Animals; Dogs; Phlebovirus; Viral Vaccines; Severe Fever with Thrombocytopenia Syndrome; Vaccines, Inactivated; Antibodies, Neutralizing; Antibodies, Viral; Dog Diseases; Viremia; Viral Load; Spleen; Adjuvants, Immunologic; Vaccination
PubMed: 38635002
DOI: 10.1007/s12275-024-00119-y -
PLoS Neglected Tropical Diseases Apr 2024Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver...
OBJECTIVES
Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS.
METHODS
A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks.
RESULTS
60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 μmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome.
CONCLUSIONS
Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.
Topics: Humans; Male; Female; Middle Aged; Prognosis; Severe Fever with Thrombocytopenia Syndrome; Retrospective Studies; Aged; Liver; Alkaline Phosphatase; Risk Factors; Liver Function Tests; Aspartate Aminotransferases; Adult; Phlebovirus; Alanine Transaminase; Aged, 80 and over; Proportional Hazards Models; Bilirubin
PubMed: 38626222
DOI: 10.1371/journal.pntd.0012068 -
Virulence Dec 2024MicroRNAs (miRNAs) are small non-coding RNAs that regulate the post-transcriptional expression of target genes. Virus-encoded miRNAs play an important role in the...
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the post-transcriptional expression of target genes. Virus-encoded miRNAs play an important role in the replication of viruses, modulate gene expression in both the virus and host, and affect their persistence and immune evasion in hosts. This renders viral miRNAs as potential targets for therapeutic applications, especially against pathogenic viruses that infect humans and animals. Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic RNA virus that causes severe disease in both humans and livestock. High mortality among newborn lambs and abortion storms are key characteristics of an RVF outbreak. To date, limited information is available on RVFV-derived miRNAs. In this study, computational methods were used to analyse the RVFV genome for putative pre-miRNA genes, which were then analysed for the presence of mature miRNAs. We detected 19 RVFV-encoded miRNAs and identified their potential mRNAs targets in sheep (, the most susceptible host. The identification of significantly enriched genes in association with RVFV miRNAs will help elucidate the molecular mechanisms underlying RVFV pathogenesis and potentially uncover novel drug targets for RVFV.
Topics: Humans; Pregnancy; Female; Animals; Sheep; Rift Valley fever virus; Rift Valley Fever; Culicidae; Disease Outbreaks; MicroRNAs
PubMed: 38548679
DOI: 10.1080/21505594.2024.2329447 -
The Journal of General Virology Mar 2024Rift Valley fever virus (RVFV) is an emerging arboviral disease with pandemic potential. While infection is often self-limiting, a subset of individuals may develop...
Rift Valley fever virus (RVFV) is an emerging arboviral disease with pandemic potential. While infection is often self-limiting, a subset of individuals may develop late-onset encephalitis, accounting for up to 20 % of severe cases. Importantly, individuals displaying neurologic disease have up to a 53 % case fatality rate, yet the neuropathogenesis of RVFV infection remains understudied. In this study, we evaluated whether postnatal rat brain slice cultures (BSCs) could be used to evaluate RVFV infection in the central nervous system. BSCs mounted an inflammatory response after slicing, which resolved over time, and they were viable in culture for at least 12 days. Infection of rat BSCs with pathogenic RVFV strain ZH501 induced tissue damage and apoptosis over 48 h. Viral replication in BSCs reached up to 1×10 p.f.u. equivalents/ml, depending on inoculation dose. Confocal immunofluorescent microscopy of cleared slices confirmed direct infection of neurons as well as activation of microglia and astrocytes. Further, RVFV-infected rat BSCs produced antiviral cytokines and chemokines, including MCP-1 and GRO/KC. This study demonstrates that rat BSCs support replication of RVFV for studies of neuropathogenesis. This allows for continued and complementary investigation into RVFV infection in an postnatal brain slice culture format.
Topics: Rats; Animals; Rift Valley fever virus; Rift Valley Fever; Cytokines; Brain; Cell Death
PubMed: 38546100
DOI: 10.1099/jgv.0.001970 -
Viruses Mar 2024Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that...
Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks.
Topics: Humans; Animals; Mice; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; Phlebovirus; Tick-Borne Diseases; Interferon Type I
PubMed: 38543766
DOI: 10.3390/v16030401 -
Biomedicines Feb 2024Rift Valley fever is a vector-borne zoonotic disease caused by the Rift Valley fever virus (Phlebovirus genus) listed among the eight pathogens included in the Bluepoint... (Review)
Review
Rift Valley fever is a vector-borne zoonotic disease caused by the Rift Valley fever virus (Phlebovirus genus) listed among the eight pathogens included in the Bluepoint list by the WHO. The transmission is mainly vehicled by and mosquito species. Symptoms of the disease are varied and non-specific, making clinical diagnosis often challenging, especially in the early stages. Due to the difficulty in distinguishing Rift Valley fever from other viral hemorrhagic fevers, as well as many other diseases that cause fever, an early diagnosis of the infection is important to limit its spread and to provide appropriate care to patients. To date, there is no validated point-of-care diagnostic tool. The virus can only be detected in the blood for a brief period, suggesting that molecular methods alone are not sufficient for case determination. For this, it is preferable to combine both molecular and serological tests. The wide distribution of competent vectors in non-endemic areas, together with global climate change, elicit the spread of RVFV to continents other than Africa, making surveillance activities vital to prevent or to limit the impact of human outbreaks and for a rapid identification of positive cases, making diagnosis a key factor for this achievement.
PubMed: 38540153
DOI: 10.3390/biomedicines12030540 -
Virologica Sinica Jun 2024
Topics: Cats; Humans; Animals; Phlebovirus; Beijing; Severe Fever with Thrombocytopenia Syndrome; Male; Cat Diseases; Female; China
PubMed: 38513807
DOI: 10.1016/j.virs.2024.03.006 -
PLoS Pathogens Mar 2024Rift Valley fever virus (RVFV) is a viral zoonosis that causes severe disease in ruminants and humans. The nonstructural small (NSs) protein is the primary virulence...
Rift Valley fever virus (RVFV) is a viral zoonosis that causes severe disease in ruminants and humans. The nonstructural small (NSs) protein is the primary virulence factor of RVFV that suppresses the host's antiviral innate immune response. Bioinformatic analysis and AlphaFold structural modeling identified four putative LC3-interacting regions (LIR) motifs (NSs 1-4) in the RVFV NSs protein, which suggest that NSs interacts with the host LC3-family proteins. Using, isothermal titration calorimetry, X-ray crystallography, co-immunoprecipitation, and co-localization experiments, the C-terminal LIR motif (NSs4) was confirmed to interact with all six human LC3 proteins. Phenylalanine at position 261 (F261) within NSs4 was found to be critical for the interaction of NSs with LC3, retention of LC3 in the nucleus, as well as the inhibition of autophagy in RVFV infected cells. These results provide mechanistic insights into the ability of RVFV to overcome antiviral autophagy through the interaction of NSs with LC3 proteins.
Topics: Animals; Humans; Rift Valley fever virus; Viral Nonstructural Proteins; Rift Valley Fever; Autophagy; Antiviral Agents
PubMed: 38512999
DOI: 10.1371/journal.ppat.1012093 -
Experimental Biology and Medicine... 2024Bunyamwera virus (BUNV) () has been found in Sub-Saharan Africa and demonstrated recently as cocirculating with Rift Valley Fever Virus (RVFV). Little is known regarding...
Bunyamwera virus (BUNV) () has been found in Sub-Saharan Africa and demonstrated recently as cocirculating with Rift Valley Fever Virus (RVFV). Little is known regarding the breadth of transmission modalities of Bunyamwera. Given its co-occurence with RVFV, we hypothesized the transmission system of BUNV shared similarities to the RVFV system including transmission by mosquitoes and environmentally mediated transmission through fomites and environmental contamination. We exposed mosquitoes to BUNV and evaluated their ability to transmit both vertically and horizontally. Further, we investigated the potential for a novel transmission modality via environmental contamination. We found that the LSU colony of was not competent for the virus for either horizontal or vertical transmission; but, 20% of larva exposed to virus via contaminated aquatic habitat were positive. However, transstadial clearance of the virus was absolute. Finally, under simulated temperature conditions that matched peak transmission in Rwanda, we found that BUNV was stable in both whole blood and serum for up to 28 days at higher total volume in tubes at moderate quantities (10 genome copies/mL). In addition, infectiousness of these samples was demonstrated in 80% of the replicates. At lower volume samples (in plates), infectiousness was retained out to 6-8 days with a maximum infectious titer of 10 PFU/mL. Thus, the potential for contamination of the environment and/or transmission via contaminated fomites exists. Our findings have implications for biosafety and infection control, especially in the context of food animal production.
Topics: Animals; Bunyamwera virus; Aedes; Rift Valley fever virus
PubMed: 38510492
DOI: 10.3389/ebm.2024.10114 -
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