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Clinical Microbiology and Infection :... Apr 2024
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Severe Fever with Thrombocytopenia Syndrome; Retrospective Studies; Phlebovirus; Thrombocytopenia
PubMed: 38266706
DOI: 10.1016/j.cmi.2024.01.009 -
Acta Crystallographica. Section D,... Feb 2024Phenuiviridae nucleoprotein is the main structural and functional component of the viral cycle, protecting the viral RNA and mediating the essential...
Phenuiviridae nucleoprotein is the main structural and functional component of the viral cycle, protecting the viral RNA and mediating the essential replication/transcription processes. The nucleoprotein (N) binds the RNA using its globular core and polymerizes through the N-terminus, which is presented as a highly flexible arm, as demonstrated in this article. The nucleoprotein exists in an `open' or a `closed' conformation. In the case of the closed conformation the flexible N-terminal arm folds over the RNA-binding cleft, preventing RNA adsorption. In the open conformation the arm is extended in such a way that both RNA adsorption and N polymerization are possible. In this article, single-crystal X-ray diffraction and small-angle X-ray scattering were used to study the N protein of Toscana virus complexed with a single-chain camelid antibody (VHH) and it is shown that in the presence of the antibody the nucleoprotein is unable to achieve a functional assembly to form a ribonucleoprotein complex.
Topics: Nucleoproteins; Sandfly fever Naples virus; Nucleocapsid Proteins; Models, Molecular; RNA, Viral
PubMed: 38265877
DOI: 10.1107/S2059798324000196 -
Viruses Jan 2024Wuxiang virus (WUXV) is the first sandfly-borne isolated from collected in China and has been established as a consistent viral presence in the local sandfly...
Wuxiang virus (WUXV) is the first sandfly-borne isolated from collected in China and has been established as a consistent viral presence in the local sandfly populations of both Wuxiang County and Yangquan City. However, its distribution in the Shanxi Province remains unclear. In this study, three novel WUXV strains were isolated from sandflies collected from Jiexiu City, Shanxi Province, China, in 2022. Subsequently, whole-genome sequences of these novel strains were generated using next-generation sequencing. The open reading frame (ORF) sequences of the WUXV strains from the three locations were subjected to gene analysis. Phylogenetic analysis revealed that WUXV belongs to two distinct clades with geographical differences. Strains from Wuxiang County and Yangquan City belonged to clade 1, whereas strains from Jiexiu City belonged to clade 2. Reassortment and recombination analyses indicated no gene reassortment or recombination between the two clades. However, four reassortments or recombination events could be detected in clade 1 strains. By aligning the amino acid sequences, eighty-seven mutation sites were identified between the two clades, with seventeen, sixty, nine, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Additionally, selection pressure analysis identified 17 positively selected sites across the entire genome of WUXV, with two, thirteen, one, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Notably, sites M-312 and M-340 in the M segment not only represented mutation sites but also showed positive selective pressure effects. These findings highlight the need for continuous nationwide surveillance of WUXV.
Topics: Animals; Phylogeny; China; Amino Acid Sequence; High-Throughput Nucleotide Sequencing; Psychodidae; RNA-Dependent RNA Polymerase
PubMed: 38257803
DOI: 10.3390/v16010103 -
Viruses Jan 2024Toscana virus (TOSV), a sandfly-borne virus, is an important etiological agent in human acute meningitis and meningoencephalitis in the Mediterranean area during the...
Toscana virus (TOSV), a sandfly-borne virus, is an important etiological agent in human acute meningitis and meningoencephalitis in the Mediterranean area during the summer. However, the actual number of TOSV infections is underestimated. Laboratory confirmation is necessary because TOSV infection has overlapping clinical features with other neuro-invasive viral infections. Nowadays, the reference test for direct diagnosis in the acute phase of TOSV infection is the PCR based method for detecting TOSV in cerebrospinal fluid and/or plasma, serum, or blood. Although poorly employed, urine is another helpful biological matrix for TOSV detection. Urine is a matrix rich in PCR inhibitors that affect PCR efficiency; consequently, false negatives could be generated. To investigate the potential effect of urine PCR inhibitors on TOSV detection, we compared undiluted and diluted urine using 10-fold series of spiked TOSV. The results showed a significant improvement in TOSV detection performance in diluted urine (1 TCID vs. 1 × 10 TCID limit of detection and 101.35% vs. 129.62% efficiency, respectively, in diluted and undiluted urine). In conclusion, our data provide preliminary important insights into the use of diluted urine to limit the impact of the inhibitory effects of urine on the detection of TOSV in RT-PCR-based approaches.
Topics: Humans; Sandfly fever Naples virus; Body Fluids; Plasma; Encephalitis, California; Laboratories
PubMed: 38257798
DOI: 10.3390/v16010098 -
Viruses Jan 2024Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral...
Rift Valley fever is a zoonotic viral disease transmitted by mosquitoes, impacting both humans and livestock. Currently, there are no approved vaccines or antiviral treatments for humans. This study aimed to evaluate the in vitro efficacy of chemical compounds targeting the Gc fusion mechanism. These compounds were identified through virtual screening of millions of commercially available small molecules using a structure-based artificial intelligence bioactivity predictor. In our experiments, a pretreatment with small molecule compounds revealed that 3 out of 94 selected compounds effectively inhibited the replication of the Rift Valley fever virus MP-12 strain in Vero cells. As anticipated, these compounds did not impede viral RNA replication when administered three hours after infection. However, significant inhibition of viral RNA replication occurred upon viral entry when cells were pretreated with these small molecules. Furthermore, these compounds exhibited significant inhibition against Arumowot virus, another phlebovirus, while showing no antiviral effects on tick-borne bandaviruses. Our study validates AI-based virtual high throughput screening as a rational approach for identifying effective antiviral candidates for Rift Valley fever virus and other bunyaviruses.
Topics: Chlorocebus aethiops; Humans; Animals; Rift Valley fever virus; Artificial Intelligence; Vero Cells; Computers; Phlebovirus; RNA, Viral; Antiviral Agents
PubMed: 38257788
DOI: 10.3390/v16010088 -
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 -
Zhonghua Liu Xing Bing Xue Za Zhi =... Jan 2024To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China. The incidence data of SFTS in...
To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China. The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed. From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age. From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.
Topics: Middle Aged; Humans; Female; Male; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus; Thrombocytopenia; Fever; China; Incidence; Bunyaviridae Infections
PubMed: 38228532
DOI: 10.3760/cma.j.cn112338-20230504-00274 -
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