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Viruses Jan 2024The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice...
The introduction of three single nucleotide mutations into the genome of the virulent RVFV ZH548 strain allows for the rescue of a fully attenuated virus in mice (ZH548-rA2). These mutations are located in the viral genes encoding the RdRp and the non-structural protein NSs. This paper shows the results obtained after the subcutaneous inoculation of ZH548-rA2 in adult sheep and the subsequent challenge with the parental virus (ZH548-rC1). Inoculation with the ZH548-rA2 virus caused no detectable clinical or pathological effect in sheep, whereas inoculation of the parental rC1 virus caused lesions compatible with viral infection characterised by the presence of scattered hepatic necrosis. Viral infection was confirmed via immunohistochemistry, with hepatocytes within the necrotic foci appearing as the main cells immunolabelled against viral antigen. Furthermore, the inoculation of sheep with the rA2 virus prevented the liver damage expected after rC1 virus inoculation, suggesting a protective efficacy in sheep which correlated with the induction of both humoral and cell-mediated immune responses.
Topics: Animals; Mice; Sheep; Rift Valley fever virus; Antigens, Viral; Genes, Viral; Hepatocytes; Virus Diseases
PubMed: 38257787
DOI: 10.3390/v16010087 -
Viruses Dec 2023In recent years, numerous viruses have been identified from ticks, and some have been linked to clinical cases of emerging tick-borne diseases. Chinese northeast...
In recent years, numerous viruses have been identified from ticks, and some have been linked to clinical cases of emerging tick-borne diseases. Chinese northeast frontier is tick infested. However, there is a notable lack of systematic monitoring efforts to assess the viral composition in the area, leaving the ecological landscape of viruses carried by ticks not clear enough. Between April and June 2017, 7101 ticks were collected to perform virus surveillance on the China-North Korea border, specifically in Tonghua, Baishan, and Yanbian. A total of 2127 were identified. Further investigation revealed the diversity of tick-borne viruses by transcriptome sequencing of . All ticks tested negative for tick-borne encephalitis virus. Transcriptome sequencing expanded 121 genomic sequence data of 12 different virus species from . Notably, a new segmented flavivirus, named Baishan Forest Tick Virus, were identified, closely related to Alongshan virus and Harz mountain virus. Therefore, this new virus may pose a potential threat to humans. Furthermore, the study revealed the existence of seven emerging tick-borne viruses dating back to 2017. These previously identified viruses included Mudanjiang phlebovirus, Onega tick phlebovirus, Sara tick phlebovirus, Yichun mivirus, and three unnamed viruses (one belonging to the family and the other two belonging to the family). The existence of these emerging tick-borne viruses in tick samples collected in 2017 suggests that their history may extend further than previously recognized. This study provides invaluable insights into the virome of Ixodes persulcatus in the China-North Korea border region, enhancing our ongoing efforts to manage the risks associated with tick-borne viruses.
Topics: Humans; Animals; Ixodes; Democratic People's Republic of Korea; Virome; China; RNA; Thogotovirus
PubMed: 38257762
DOI: 10.3390/v16010062 -
Frontiers in Cellular and Infection... 2023The Hedi virus (HEDV) and Wuxiang virus (WUXV) are newly discovered Bunyaviruses transmitted by sandflies. The geographical distribution of isolation of these two...
INTRODUCTION
The Hedi virus (HEDV) and Wuxiang virus (WUXV) are newly discovered Bunyaviruses transmitted by sandflies. The geographical distribution of isolation of these two viruses continues to expand and it has been reported that WUXV causes neurological symptoms and even death in suckling mice. However, little is known about the prevalence of the two viruses in mammalian infections.
METHODS
In order to understand the infection status of HEDV and WUXV in humans and animals from regions where the viruses have been isolated, this study used Western blotting to detect the positive rates of HEDV and WUXV IgG antibodies in serum samples from febrile patients, dogs, and chickens in the forementioned regions.
RESULTS
The results showed that of the 29 human serum samples, 17.24% (5/29) tested positive for HEDV, while 68.96% (20/29) were positive for WUXV. In the 31 dog serum samples, 87.10% (27/31) were positive for HEDV and 70.97% (22/31) were positive for WUXV, while in the 36 chicken serum samples, 47.22% (17/36) were positive for HEDV, and 52.78% (19/36) were positive for WUXV.
DISCUSSION
These findings suggest there are widespread infections of HEDV and WUXV in mammals (dogs, chickens) and humans from the regions where these viruses have been isolated. Moreover, the positive rate of HEDV infections was higher in local animals compared to that measured in human specimens. This is the first seroepidemiological study of these two sandfly-transmitted viruses. The findings of the study have practical implications for vector-borne viral infections and related zoonotic infections in China, as well as providing an important reference for studies on the relationship between sandfly-transmitted viruses and zoonotic infections outside of China.
Topics: Humans; Animals; Dogs; Mice; Psychodidae; Sandfly fever Naples virus; Chickens; Phlebotomus; Zoonoses; Mammals; Antibodies, Viral; China
PubMed: 38235489
DOI: 10.3389/fcimb.2023.1291937 -
Ticks and Tick-borne Diseases Mar 2024Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a crucial role in the defense against SFTSV; however, the impact of viral propagation of STFSV on the innate immune system remains unclear. Although proteomics analysis revealed that the expression of the downregulator of transcription 1 (DR1) increased after SFTSV infection, the specific change trend and the functional role of DR1 during viral infection remain unelucidated. In this study, we demonstrate that DR1 was highly expressed in response to SFTSV infection in HEK 293T cells using qRT-PCR and Western blot analysis. Furthermore, viral replication significantly increased the expression of various TLRs, especially TLR9. Our data indicated that DR1 positively regulated the expression of TLRs in HEK 293T cells, DR1 overexpression highly increased the expression of numerous TLRs, whereas RNAi-mediated DR1 silencing decreased TLR expression. Additionally, the myeloid differentiation primary response gene 88 (MyD88)-dependent or TIR-domain-containing adaptor inducing interferon-β (TRIF)-dependent signaling pathways were highly up- and downregulated by the overexpression and silencing of DR1, respectively. Finally, we report that DR1 stimulates the expression of TLR7, TLR8, and TLR9, thereby upregulating the TRIF-dependent and MyD88-dependent signaling pathways during the SFTSV infection, attenuating viral replication, and enhancing the production of type I interferon and various inflammatory factors, including IL-1β, IL-6, and IL-8. These results imply that DR1 defends against SFTSV replication by inducing the expression of TLR7, TLR8, and TLR9. Collectively, our findings revealed a novel role and mechanism of DR1 in mediating antiviral responses and innate immunity.
Topics: Animals; Humans; Adaptor Proteins, Vesicular Transport; Down-Regulation; HEK293 Cells; Myeloid Differentiation Factor 88; Phosphoproteins; Signal Transduction; Toll-Like Receptor 7; Toll-Like Receptor 8; Toll-Like Receptor 9; Transcription Factors; Phlebovirus; Bunyaviridae Infections
PubMed: 38194758
DOI: 10.1016/j.ttbdis.2023.102307 -
EBioMedicine Feb 2024
Topics: Humans; Biology; Phlebovirus
PubMed: 38194743
DOI: 10.1016/j.ebiom.2024.104968 -
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 -
The Journal of Veterinary Medical... Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonotic disease, endemic to Asian regions, including western Japan. Cats appear to...
Severe fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonotic disease, endemic to Asian regions, including western Japan. Cats appear to suffer a particularly severe form of the disease; however, feline SFTS is not clinically well characterized. Accordingly, in this study, we investigated the associations of, demographic, hematological and biochemical, immunological, and virological parameters with clinical outcome (fatal cases vs. survivors) in SFTSV-positive cats. Viral genomic analysis was also performed. Viral load in blood, total bilirubin, creatine phosphokinase, serum amyloid A, interleukin-6, tumor necrotic factor-α, and virus-specific IgM and IgG differed significantly between survivors and fatal cases, and thus may have utility as prognosticators. Furthermore, survivor profiling revealed high-level of viremia with multiple parameters (white blood cells, platelet, total bilirubin, glucose, and serum amyloid A) beyond the reference range in the 7-day acute phase, and signs of clinical recovery in the post-acute phase (parameters returning to, or tending toward, the reference range). However, SFTSV was still detectable from some survived cats even 14 days after onset of disease, indicating the risk of infection posed by close-contact exposure may persist through the post-acute phase. This study provides useful information for prognostic assessments of acute feline SFTS, and may contribute to early treatment plans for cats with SFTS. Our findings also alert pet owners and animal health professionals to the need for prolonged vigilance against animal-to-human transmission when handling cats that have been diagnosed with SFTS.
Topics: Animals; Humans; Cats; Severe Fever with Thrombocytopenia Syndrome; Prognosis; Phlebovirus; Bunyaviridae Infections; Serum Amyloid A Protein; Tick-Borne Diseases; Bilirubin; Cat Diseases
PubMed: 38171741
DOI: 10.1292/jvms.22-0427 -
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 -
The Journal of Veterinary Medical... Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a tick-borne virus called severe fever with thrombocytopenia syndrome virus...
Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a tick-borne virus called severe fever with thrombocytopenia syndrome virus (SFTSV). In recent years, human infections through contact with ticks and through contact with the bodily fluids of infected dogs and cats have been reported; however, no vaccine is currently available. SFTSV has two glycoproteins (Gn and Gc) on its envelope, which are vaccine-target antigens involved in immunogenicity. In the present study, we constructed novel SFTS vaccine candidates using an adeno-associated virus (AAV) vector to transport the SFTSV glycoprotein genome. AAV vectors are widely used in gene therapy and their safety has been confirmed in clinical trials. Recently, AAV vectors have been used to develop influenza and SARS-CoV-2 vaccines. Two types of vaccines (AAV9-SFTSV Gn and AAV9-SFTSV Gc) carrying SFTSV Gn and Gc genes were produced. The expression of Gn and Gc proteins in HEK293T cells was confirmed by infection with vaccines. These vaccines were inoculated into mice, and the collected sera produced anti-SFTS antibodies. Furthermore, sera from AAV9-SFTSV Gn infected mice showed a potent neutralizing ability, similar to previously reported SFTS vaccine candidates that protected animals from SFTSV infection. These findings suggest that this vaccine is a promising candidate for a new SFTS vaccine.
Topics: Animals; Humans; Cats; Mice; Dogs; Severe Fever with Thrombocytopenia Syndrome; Dependovirus; Phlebovirus; Bunyaviridae Infections; COVID-19 Vaccines; Cat Diseases; HEK293 Cells; Dog Diseases; Glycoproteins; Thrombocytopenia; Rodent Diseases
PubMed: 38143087
DOI: 10.1292/jvms.23-0375 -
Viruses Dec 2023Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). In Thailand, three human cases of SFTS...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). In Thailand, three human cases of SFTS were reported in 2019 and 2020, but there was no report of SFTSV infection in animals. Our study revealed that at least 16.6% of dogs in Thailand were seropositive for SFTSV infection, and the SFTSV-positive dogs were found in several districts in Thailand. Additionally, more than 70% of the serum samples collected at one shelter possessed virus-neutralization antibodies against SFTSV and the near-complete genome sequences of the SFTSV were determined from one dog in the shelter. The dog SFTSV was genetically close to those from Thailand and Chinese patients and belonged to genotype J3. These results indicated that SFTSV has already spread among animals in Thailand.
Topics: Animals; Humans; Dogs; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; Seroepidemiologic Studies; Thailand; Antibodies, Viral; Phlebovirus; Tick-Borne Diseases
PubMed: 38140644
DOI: 10.3390/v15122403