Biology subjects

TANURI, A.

Publications and source records attributed to TANURI, A..

4 recordsLinked to original sources

bioRxiv2026

Zika virus oncolytic signaling reverts immunosuppressive and angiogenic glioblastoma microenvironment in vitro and in vivo

Glioblastoma (GBM), the most aggressive primary brain tumor, remains refractory to conventional therapies, characterized by high relapse rates and poor clinical prognosis. Oncolytic viruses represent a promising therapeutic frontier; specifically, Zika virus (ZIKV) has shown potent oncolytic activity against GBM in vitro and in vivo. However, its impact on the tumor microenvironment (TME) remains poorly understood. Here, we demonstrate that ZIKV modulates pivotal TME components, triggering paracrine anti-angiogenic signaling that impairs endothelial stabilization and reprogramming microglia toward an anti-tumoral phenotype. These findings were corroborated in vivo in GBM-bearing mice. Using unbiased RNA-Seq, we identified type III interferon (IFN) signaling as the primary mediator of this ZIKV-induced TME remodeling. Crucially, analysis of human glioma datasets revealed that the type III IFN receptor complex is highly expressed in patients, identifying a high-risk population equipped with the molecular machinery to respond to this axis. Exogenous treatment with type III IFN in vitro and in vivo successfully mimicked ZIKV's anti-tumoral effects, reducing angiogenesis and promoting immune activation. Our results demonstrate that ZIKV acts as an immunotherapeutic agent capable of shifting the TME toward an anti-tumoral state, highlighting the type III IFN pathway as an actionable vulnerability and a promising strategy for patients failing conventional therapies.

cancer biology↗

bioRxiv2023

Saxitoxin potentiates Zika virus-induced cell death in human neurons but not in neural progenitors and astrocytes

The Zika virus (ZIKV) outbreak in Brazil between 2015 and 2016 was associated with an increased prevalence of severe congenital malformations, including microcephaly. Notably, the distribution of microcephaly cases was not uniform across the country, with a disproportionately higher incidence recorded in the Northeast region (NE). Our previous work demonstrated that saxitoxin (STX), a toxin ubiquitously present in the drinking water reservoirs of the NE, exacerbated the damaging effects of ZIKV on the developing brain. In the present study, we hypothesized that STXs impact might vary among different neural cell types. Our experimental observations suggest that exposure to STX potentiates the neurotoxic effect of Zika Virus (ZIKV) on human neuronal cells. However, while ZIKV infection demonstrated severe impacts on astrocytes and neural stem cells (NSCs), the addition of STX did not exacerbate these effects. We observed that neurons subjected to STX exposure were more prone to apoptosis and displayed a higher number of ZIKV-infected cells. These findings suggest that STX exacerbates the harmful effects of ZIKV on neurons, thereby providing a plausible explanation for the heightened severity of ZIKV-induced congenital malformations observed in Brazils NE. This study underscores the importance of understanding the interactive effects of environmental toxins and infectious pathogens on neural development, with potential implications for public health policies and interventions.

neuroscience↗

bioRxiv2022

Discovery of two novel Torque Teno viruses in Callithrix penicillata provides insights on Anelloviridae diversification dynamics

1.The development of high throughput sequencing (HTS) technologies and metagenomics protocols deeply impacted the discovery of viral diversity. Moreover, the comprehension of evolution and immunology of the Neotropical primates (NP) and their susceptibility to infectious diseases are central for the characterization of the scope of etiological agents that may impact global health, due to their evolutionary proximity to Old World primates, including humans. In the present work, novel anelloviruses were detected and characterized through HTS protocols in the NP Callithrix penicillata, the common black-tufted marmoset. De novo assembly of generated sequences was carried out and a total of 15 contigs were identified with complete Anelloviridae ORF1 gene, two of them including a flanking GC-rich region, confirming the presence of two whole novel genomes of ~3kb. The identified viruses were monophyletic within the Epsilontorquevirus genus, a lineage harboring previously reported anelloviruses infecting hosts from the Cebidae family. The genetic divergence found in the new viruses characterized two novel species, named Epsilontorquevirus callithrichensis I and II. The phylogenetic pattern inferred for the Epsilontorquevirus genus was consistent with the topology of their host species tree, echoing a virus-host diversification model observed in other viral groups. This study expands the host span of Anelloviridae and provides insights into their diversification dynamics, highlighting the importance of sampling animal viral genomes to obtain a clearer depiction of their long-term evolutionary processes.

genetics↗

bioRxiv2020

Equine hyperimmune globulin raised against the SARS-CoV-2 spike glycoprotein has extremely high neutralizing titers

We used the trimeric spike (S) glycoprotein (residues 1-1208) in the prefusion conformation to immunize horses for production of hyperimmune globulins against SARS-CoV-2. Serum antibody titers measured by anti-spike ELISA were above 1:1,000,000, and neutralizing antibody titer was 1:14,604 (average PRNT90), which is 140-fold higher than the average neutralizing titer of plasma from three convalescent COVID-19 patients analyzed for comparison. Using the same technology routinely used for industrial production of other horse hyperimmune products, plasma from immunized animals was pepsin digested to remove the Fc portion and purified, yielding a F(ab)2 preparation with PRNT90 titers 150-fold higher than the neutralizing titers in human convalescent plasma. Repeating the hyperimmunization in a second group of horses confirmed the very high neutralizing titers in serum and in a GMP clinical F(ab)2 lot. Virus-neutralizing activity in samples from mice that received the F(ab)2 preparation was detected even three days after injection, indicating an appropriate half-life for therapeutic intervention. These results supported the design of a clinical trial (identifier NCT04573855) to evaluate safety and efficacy of this horse F(ab)2 preparation.

immunology↗