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Biology subjects

Sartori, A.

Publications and source records attributed to Sartori, A..

3 recordsLinked to original sources

Shamonda virus EU1 in Northern Italy, August 2026.

Background Following the emergence of a novel Shamonda-like virus (SHAV) in Europe, suspected clinical cases in dairy cattle were reported in Northeastern Italy. Investigation was required in dairy cattle in Northeastern Italy. Methods Samples were collected from 28 farms displaying fever and reduced milk yield and were screened using molecular methods (PanSimbu real-time RT-PCR followed by Sanger sequencing and differential PCRs for SBV/BTV). Positive samples were subsequently confirmed by Sanger sequencing and selected samples underwent whole-genome sequencing using a metagenomic approach. Results Twenty-four among sera and blood samples from 12 farms tested positive for SHAV. WGS confirmed that Italian strains share maximum identity with the European SHAV-EU1 clade. Limitations This study concerns the results of clinical investigations on suspected cases in the two autonomous provinces of Trento and Bolzano. At present, it is not possible to infer on the circulation of the virus in other Italian provinces. Conclusions This study documents the first detection and genetic characterization of SHAV-EU1 in Italian cattle, indicating active circulation of this virus across Europe. Its identification in two north-eastern Italian provinces does not rule out wider, undetected circulation. In this regard, assessing its geographical extent requires careful evaluation, just as much remains to be discovered about its host range and the severity of symptoms.

microbiology↗

Sec61 translocon inhibitor Flavitransin blocks selectively dengue virus polyprotein insertion into the ER membrane with pan-flavivirus antiviral potency

Flavivirus infections by Dengue and Zika virus impose a significant healthcare threat worldwide. At present no FDA-approved specific antiviral treatment is available, and the safety of a vaccine against Dengue virus is still under debate. Here, we report the identification of the CADA derivative flavitransin (FT), with potent activity against DENV serotype 2 in various cell types. Moreover, FT showed consistent anti-flaviviral activity against all four DENV serotypes, and also against Zika and Yellow fever virus. Viral polyprotein biogenesis was completely abolished by FT treatment of DENV-infected cells. Drug profiling by a-time-of-drug-addition assay revealed a post-entry antiviral effect of FT, in line with its anticipated Sec61 inhibitory effect. Subsequent analysis of the individual viral proteins in transfected HEK293T cells indicated that FT suppresses the expression of the structural proteins (pre-membrane and envelope) only. Furthermore, cell free in vitro protein translation analysis demonstrated a direct inhibitory effect of FT on the co-translational translocation of the DENV polyprotein across the ER membrane. More specifically, FT inhibited the initiation of protein translocation into the ER that relies on the N-terminal transmembrane region of the capsid subunit of the DENV polyprotein, resulting in rerouting of the viral pre-protein to the cytosol for proteasomal degradation. Finally, selection and genotyping of FT-resistant HCT116 cells revealed a unique A70V mutation in the Sec61 subunit that conferred resistance to FT in infected cells. Long-term exposure of DENV to FT demonstrated a high barrier to resistance development. In conclusion, our data demonstrate that FT selectively interferes with the initiation of ER co-translational translocation of the DENV polyprotein and confirm the critical role of this translocation process in the flavivirus replication cycle.

microbiology↗

Improving Leukemic CD34+/CD38- Blasts Characterization With Single-Cell Transcriptome Sequencing

SUMMARY / ABSTRACTAcute myeloid leukemia (AML) is a particularly aggressive blood cancer that is difficult to treat because of the incomplete eradication of rare blast cells that possess self-renewal and leukemia-initiating properties. To characterize resistant blasts, we analyzed for the first time the transcriptomes of individual CD34+/CD38- blasts by single-cell mRNA sequencing of 359 CD33+/CD34+/CD38-/+ sorted cells from two patients with AML and four unaffected individuals. We demonstrated that the captured blasts possess the transcriptomic hallmarks of self-renewal and leukemia-initiating ability. The effects of somatic mutations on the cancer cells are visible at the transcriptional level, and the cellular signaling pathway activity of the blasts is altered, revealing disease-associated gene networks. We also identified a core set of transcription factors that were co-activated in blasts, which suggests a joint transcription program among blasts. Finally, we revealed that leukemogenesis and putative prognostic gene-expression signatures are present at diagnosis in leukemic CD33+/CD34+/CD38- cells and can be detected using a single-cell RNA sequencing approach.

cancer biology↗