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Journal of Virology Feb 2022Rift Valley fever virus (RVFV) belongs to the order and is the type species of genus , which accounts for over 50% of family species. RVFV is mosquito-borne and causes...
Rift Valley fever virus (RVFV) belongs to the order and is the type species of genus , which accounts for over 50% of family species. RVFV is mosquito-borne and causes severe diseases in both humans and livestock, and consists of three segments (S, M, L) in the genome. The L segment encodes an RNA-dependent RNA polymerase (RdRp, L protein) that is responsible for facilitating the replication and transcription of the virus. It is essential for the virus and has multiple drug targets. Here, we established an expression system and purification procedures for full-length L protein, which is composed of an endonuclease domain, RdRp domain, and cap-binding domain. A cryo-EM L protein structure was reported at 3.6 Å resolution. In this first L protein structure of genus , the priming loop of RVFV L protein is distinctly different from those of other L proteins and undergoes large movements related to its replication role. Structural and biochemical analyses indicate that a single template can induce initiation of RNA synthesis, which is notably enhanced by 5' viral RNA. These findings help advance our understanding of the mechanism of RNA synthesis and provide an important basis for developing antiviral inhibitors. The zoonosis RVF virus (RVFV) is one of the most serious arbovirus threats to both human and animal health. RNA-dependent RNA polymerase (RdRp) is a multifunctional enzyme catalyzing genome replication as well as viral transcription, so the RdRp is essential for studying the virus and has multiple drug targets. In our study, we report the structure of RVFV L protein at 3.6 Å resolution by cryo-EM. This is the first L protein structure of genus . Strikingly, a single template can initiate RNA replication. The structure and assays provide a comprehensive and in-depth understanding of the catalytic and substrate recognition mechanism of RdRp.
Topics: Amino Acid Motifs; Catalytic Domain; Chemical Phenomena; Conserved Sequence; Cryoelectron Microscopy; Models, Molecular; Protein Conformation; Protein Interaction Domains and Motifs; RNA-Dependent RNA Polymerase; Recombinant Fusion Proteins; Rift Valley fever virus; Viral Proteins
PubMed: 34787453
DOI: 10.1128/JVI.01713-21 -
Infectious Diseases of Poverty Jul 2022Viral pathogens belonging to the order Bunyavirales pose a continuous background threat to global health, but the fact remains that they are usually neglected and their...
BACKGROUND
Viral pathogens belonging to the order Bunyavirales pose a continuous background threat to global health, but the fact remains that they are usually neglected and their distribution is still ambiguously known. We aim to map the geographical distribution of Bunyavirales viruses and assess the environmental suitability and transmission risk of major Bunyavirales viruses in China.
METHODS
We assembled data on all Bunyavirales viruses detected in humans, animals and vectors from multiple sources, to update distribution maps of them across China. In addition, we predicted environmental suitability at the 10 km × 10 km pixel level by applying boosted regression tree models for two important Bunyavirales viruses, including Crimean-Congo hemorrhagic fever virus (CCHFV) and Rift Valley fever virus (RVFV). Based on model-projected risks and air travel volume, the imported risk of RVFV was also estimated from its endemic areas to the cities in China.
RESULTS
Here we mapped all 89 species of Bunyavirales viruses in China from January 1951 to June 2021. Nineteen viruses were shown to infect humans, including ten species first reported as human infections. A total of 447,848 cases infected with Bunyavirales viruses were reported, and hantaviruses, Dabie bandavirus and Crimean-Congo hemorrhagic fever virus (CCHFV) had the severest disease burden. Model-predicted maps showed that Xinjiang and southwestern Yunnan had the highest environmental suitability for CCHFV occurrence, mainly related to Hyalomma asiaticum presence, while southern China had the highest environmental suitability for Rift Valley fever virus (RVFV) transmission all year round, mainly driven by livestock density, mean precipitation in the previous month. We further identified three cities including Guangzhou, Beijing and Shanghai, with the highest imported risk of RVFV potentially from Egypt, South Africa, Saudi Arabia and Kenya.
CONCLUSIONS
A variety of Bunyavirales viruses are widely distributed in China, and the two major neglected Bunyavirales viruses including CCHFV and RVFV, both have the potential for outbreaks in local areas of China. Our study can help to promote the understanding of risk distribution and disease burden of Bunyavirales viruses in China, and the risk maps of CCHFV and RVFV occurrence are crucial to the targeted surveillance and control, especially in seasons and locations at high risk.
Topics: Animals; China; Hemorrhagic Fever Virus, Crimean-Congo; Ixodidae; Kenya; Rift Valley fever virus
PubMed: 35799306
DOI: 10.1186/s40249-022-00993-x -
Emerging Infectious Diseases May 2021We describe a series of severe neuroinvasive infections caused by Toscana virus, identified by real-time reverse transcription PCR testing, in 8 hospitalized patients in...
We describe a series of severe neuroinvasive infections caused by Toscana virus, identified by real-time reverse transcription PCR testing, in 8 hospitalized patients in Bucharest, Romania, during the summer seasons of 2017 and 2018. Of 8 patients, 5 died. Sequencing showed that the circulating virus belonged to lineage A.
Topics: Bunyaviridae Infections; Humans; Romania; Sandfly fever Naples virus
PubMed: 33900182
DOI: 10.3201/eid2705.204598 -
Viruses Jan 2021Phleboviruses transmitted by phlebotomine sandflies are endemic in the Mediterranean basin. (TOSV), (SFSV), and (SFNV) are responsible of summer fever, with...
Phleboviruses transmitted by phlebotomine sandflies are endemic in the Mediterranean basin. (TOSV), (SFSV), and (SFNV) are responsible of summer fever, with well-known pathogenic potential for humans ranging from asymptomatic to mild fever, in addition to neuro-invasive infections during summer. Although TOSV, in particular, is a significant and well-known human pathogen, SFVs remain neglected, with many gaps in the relevant knowledge. Sero-epidemiological studies and case reports recently showed a geographical wider distribution than previously considered, although the real incidence of phleboviruses infections in the Mediterranean area is still unknown. Here we retrospectively evaluated the circulation of phleboviruses during summer seasons between 2007 and 2019 in 649 patients showing neurological symptoms using both molecular and serological approaches. We found that 42/649 (6.5%) subjects experienced phlebovirus infection and only 10/42 cases were detected by molecular assays, whereas the other 32/42 were identified using serological approaches, including neutralization assays. During the 2013 summer, an outbreak in the Lombardy region is described because the prevalence of phlebovirus infection reached 37.2% (19/51 subjects). Interestingly, only 5/19 (26.5%) reported traveling in endemic areas. Of note, no cross-neutralization was observed between different strains tested, showing the possibility to be reinfected by newly discovered phlebovirus strains. In conclusion, phlebovirus infections are still inadequately considered by physicians and are generally underestimated. However, based on our results, sandfly fever viruses should be routinely included in diagnostic panels during summer period, including in Northern Italy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Neutralizing; Female; Humans; Immunoglobulin G; Immunoglobulin M; Italy; Male; Middle Aged; Phlebotomus Fever; Phlebovirus; RNA, Viral; Retrospective Studies; Seasons; Young Adult
PubMed: 33573092
DOI: 10.3390/v13020209 -
Microbiology Spectrum Oct 2022Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious...
Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious diseases in humans or animals, potentially imposing significant public health burdens and threats to the husbandry industry. Therefore, identifying the profiles of tick-borne viruses will provide valuable information about the evolution and pathogen ecology of tick-borne viruses. In this study, we investigated the viromes of parasitic ticks collected from the body surfaces of herbivores in Xinjiang Uyghur Autonomous Region and Inner Mongolia Autonomous Region of China, two regions in northwest China. By using a metatranscriptomic approach, 17 RNA viruses with high diversity in genomic organization and evolution were identified. Among them, nine are proposed to be novel species. The classified viruses belonged to six viral families, including , , , , , and , and unclassified viruses were also identified. In addition, although some viruses from different sampling locations shared significant similarities, the abundance and diversity of viruses notably varied among the different collection locations. This study demonstrates the diversity of tick-borne viruses in Xinjiang and Inner Mongolia and provides informative data for further study of the evolution and pathogenicity of these RNA viruses. Ticks are widely distributed in pastoral areas in northwestern China and act as vectors that carry and transmit a variety of pathogens, especially viruses. Our study revealed the diversity of tick viruses in Xinjiang and Inner Mongolia and uncovered the phylogenetic relationships of some RNA viruses, especially the important zoonotic tick-borne severe fever with thrombocytopenia syndrome virus in Inner Mongolia. These data suggest a complex and diverse evolutionary history and potential ecological factors associated with pathogenic viruses. The pathogenicity of these tick-borne viruses currently remains unclear. Therefore, future research should focus on evaluating the transmissability and pathogenicity of these tick-borne viruses.
Topics: Humans; Animals; Ticks; Phylogeny; Virome; Phlebovirus; RNA Viruses; China; Viruses; Tick-Borne Diseases
PubMed: 36214702
DOI: 10.1128/spectrum.01115-22 -
The Journal of Biological Chemistry Jun 2023Severe fever with thrombocytopenia syndrome virus (SFTSV), which has been reported in China, Korea, Japan, Vietnam, and Taiwan, is a causative agent of severe fever...
Severe fever with thrombocytopenia syndrome virus (SFTSV), which has been reported in China, Korea, Japan, Vietnam, and Taiwan, is a causative agent of severe fever thrombocytopenia syndrome. This virus has a high mortality and induces thrombocytopenia and leukocytopenia in humans, cats, and aged ferrets, whereas immunocompetent adult mice infected with SFTSV never show symptoms. Anti-SFTSV antibodies have been detected in several animals-including goats, sheep, cattle, and pigs. However, there are no reports of severe fever thrombocytopenia syndrome in these animals. Previous studies have reported that the nonstructural protein NSs of SFTSV inhibits the type I interferon (IFN-I) response through the sequestration of human signal transducer and activator of transcription (STAT) proteins. In this study, comparative analysis of the function of NSs as IFN antagonists in human, cat, dog, ferret, mouse, and pig cells revealed a correlation between pathogenicity of SFTSV and the function of NSs in each animal. Furthermore, we found that the inhibition of IFN-I signaling and phosphorylation of STAT1 and STAT2 by NSs depended on the binding ability of NSs to STAT1 and STAT2. Our results imply that the function of NSs in antagonizing STAT2 determines the species-specific pathogenicity of SFTSV.
Topics: Aged; Animals; Cattle; Dogs; Humans; Mice; Ferrets; Interferon Type I; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Sheep; Signal Transduction; Swine; Thrombocytopenia; Viral Nonstructural Proteins
PubMed: 37187292
DOI: 10.1016/j.jbc.2023.104819 -
Nucleic Acids Research Feb 2023Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 Å. We identify how the L protein binds the 5' viral RNA in a hook-like conformation and show how the distal 5' and 3' RNA ends form a duplex positioning the 3' RNA terminus in the RdRp active site ready for initiation. We also observe the L protein stalled in the early and late stages of elongation with the RdRp core accommodating a 10-bp product-template duplex. This duplex ultimately splits with the template binding to a designated 3' secondary binding site. The structural data and observations are complemented by in vitro biochemical and cell-based mini-replicon assays. Altogether, our data provide novel key insights into the mechanism of viral genome replication by the SFTSV L protein and will aid drug development against segmented negative-strand RNA viruses.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Cryoelectron Microscopy; RNA, Viral; RNA-Dependent RNA Polymerase; Phlebovirus; Virus Replication; Genome, Viral
PubMed: 36651274
DOI: 10.1093/nar/gkac1249 -
Preventive Veterinary Medicine Sep 2022Transboundary pathogens of goats present significant constraints to the livelihoods of millions of farmers in countries such as Zambia. Consequently, this study aimed to...
Transboundary pathogens of goats present significant constraints to the livelihoods of millions of farmers in countries such as Zambia. Consequently, this study aimed to investigate the seroprevalence of Mycoplasma capricolum subsp. capripneumoniae (Mccp), foot and mouth disease virus (FMDV), Brucella spp., Crimean Congo haemorrhagic fever virus (CCHFV), and Rift Valley fever virus (RVFV) in Zambian goats. Another aim was to identify associations between seroprevalence and different predictor variables, such as trade and border proximity. From September to October 2019, 962 serum samples were collected from goats in seven Zambian districts, four of which have an international border while the remaining three do not. A questionnaire survey was conducted with each household, focusing on trade routines, management strategies and herd disease history. Animal-level seroprevalence adjusted for herd-level clustering was 8.2 % (95 % confidence interval [CI] 7.5-9.0) for Mccp, 12.9% (95% CI 12.0-13.7) for FMDV, 13.0 % (95% CI 12.1-13.9) for Brucella spp., 3.3 % (95% CI 2.8-3.7) for CCHFV, and 0.4 % (95 % CI 0.3-0.7) for RVFV. The association between herd-level seroprevalence and border proximity and trade appeared negligible, with the exception of selling goats at least twice a year which was identified as a potential risk factor for Brucella spp. (OR 4.1, 95 % CI 1.1-16.0, p = 0.040). In addition, a positive association between herd-level seroprevalence of FMDV and a herd size of 21 goats or more (OR 3.3, 95 % CI 1.0-11.1, p = 0.049) was detected. Also, positive associations between animal-level seroprevalence of Brucella spp. and increasing age (OR 7.7, 95 % CI 1.5-40.7, p = 0.016), and CCHFV and keeping pigs in the household (OR 2.7, 95 % CI 1.0-7.1, p = 0.044), were found. For FMDV (OR 3.8, 95 % CI 1.4-10.9, p = 0.011) and Brucella spp. (OR 4.5, 95 % CI 1.2-17.3, p = 0.031) on the other hand, animal-level seroprevalence was significantly higher in households without pigs. To the best of the authors' knowledge, this is the first study to describe the presence of antibodies for CCPP and CCHF in the Zambian goat population. While the association between seroprevalence and trade and border proximity generally appeared negligible, it is recommended that their influence is further evaluated in future studies, preferably through in-depth longitudinal studies incorporating impacts of different biosecurity measures and trade variations, linked to for example seasonality and trade peaks.
Topics: Animal Diseases; Animals; Brucella; Goat Diseases; Goats; Hemorrhagic Fever Virus, Crimean-Congo; Hemorrhagic Fever, Crimean; Mycoplasma; Pleuropneumonia, Contagious; Rift Valley fever virus; Seroepidemiologic Studies; Swine; Swine Diseases; Zambia
PubMed: 35835047
DOI: 10.1016/j.prevetmed.2022.105708 -
Protein & Cell Dec 2023
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus
PubMed: 37038326
DOI: 10.1093/procel/pwad019 -
Nature Communications Jul 2023Rift Valley fever virus (RVFV) is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. Outbreaks lead to high...
Rift Valley fever virus (RVFV) is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. Outbreaks lead to high rates of miscarriages in domesticated livestock. Women are also at risk of vertical virus transmission and late-term miscarriages. MAb RVFV-268 is a highly potent recombinant neutralizing human monoclonal antibody that targets RVFV. Here we show that mAb RVFV-268 reduces viral replication in rat placenta explant cultures and prevents vertical transmission in a rat model of congenital RVF. Passive transfer of mAb RVFV-268 from mother to fetus occurs as early as 6 h after administration and persists through 24 h. Administering mAb RVFV-268 2 h prior to RVFV challenge or 24 h post-challenge protects the dams and offspring from RVFV infection. These findings support mAb RVFV-268 as a pre- and post-infection treatment to subvert RVFV infection and vertical transmission, thus protecting the mother and offspring.
Topics: Pregnancy; Animals; Humans; Rats; Female; Rift Valley fever virus; Antibodies, Neutralizing; Rift Valley Fever; Abortion, Spontaneous; Antibodies, Viral; Livestock
PubMed: 37495594
DOI: 10.1038/s41467-023-40187-z