Biology subjects

Silva, P.

Publications and source records attributed to Silva, P..

17 recordsLinked to original sources

bioRxiv2026

BOWIe: Wireless Headstage for Optical Stimulation in Closed-Loop Optogenetics Experiments in Freely-moving Rodents

Optogenetics is an invaluable technique in neuroscience to study brain circuits, but conventional optogenetic systems use tethered approaches to deliver light to the brain which can hinder natural behavior. Optoelectronic advances led to the development of wireless optical stimulators for optogenetics experiments, but most reported devices have low widespread use due to complex builds and reduced versatility, which has also limited their integration in closed-loop systems. Here, we developed BOWIe, a battery-powered, low-weight, wireless headstage for photostimulation in optogenetics experiments with rodents, especially designed for simple integration in multiple behavioral setups, including those requiring closed-loop operation. BOWIe is based on a Bluetooth-Low Energy system-on-a-chip that allows simultaneous control and communication capabilities with a reduced number of components, and can be paired with an Arduino-based transmitter for simple integration in any behavioral paradigm using analogue or digital triggers. Two modes of optical stimulation are possible, either with ferrule-coupled optical fibers or LED neural probes, which permit adapting the headstage according to material availability or experimental demands. A user-friendly app was also developed to simplify headstage pairing, definition of stimulation parameters, and protocol design. BOWIe was validated in two behavioral paradigms, including in a closed-loop experiment using computer vision, Bonsai RX, and Deeplabcut Live to track behavioral parameters online and remotely trigger photostimulation upon detected events. BOWIe's modular design and flexible integration with behavioral setups make it a practical tool for in vivo experiments with optogenetics.

bioengineering↗

bioRxiv2026

Mitochondrial cytochrome c accumulation accompanies reduced electron flux through complex IV without enhancing cell sensitivity to apoptosis

We show that chronic impairment of mitochondrial respiration is associated with marked accumulation of cytochrome c (Cytc) protein. Using SCO2-deficient HCT116 cells lacking functional cytochrome c oxidase and wild-type cells exposed to sustained hypoxia, we found that substantial mitochondrial Cytc accumulation parallels reduced electron flux through Cytc. SCO2-deficient cells exhibited equally elevated Cytc levels under normoxia (19% O2) and hypoxia (0.1-3% O2). Wild-type cells under sustained hypoxia accumulated Cytc, reaching levels comparable to those in SCO2-deficient cells. This effect was reversible upon reoxygenation. Increased Cytc protein levels were also observed in other cell models, including primary cortical neurons cultured under chronic hypoxia and in cerebral cortex tissue from hypoxia-exposed mice. Cytc accumulation occurred independently of CYCS transcription, mRNA translation, HIF activation, ROS production and changes in mitochondrial network. Pharmacological inhibition of complex III was likewise accompanied by increased Cytc levels, whereas mitochondrial uncoupling had no effect, suggesting that impaired electron transfer rather than membrane depolarisation per se underlies this association. Raman spectroscopy revealed enrichment of reduced Cytc and an increased Cytc-to-cytochrome b ratio in respiration-deficient cells. Further supporting a stabilisation-based mechanism, the fraction of membrane-unbound ferro-Cytc was decreased in SCO2-deficient cells, consistent with moderate cardiolipin enrichment, which is known to enhance retention of Cytc at the inner mitochondrial membrane. Despite elevated mitochondrial Cytc content, SCO2-deficient cells were less susceptible to apoptosis induced by intermittent hypoxia or dichloroacetate. Together, these findings indicate that reduced electron flux through complex IV is associated with Cytc accumulation through increased protein stability and membrane retention without enhancing apoptotic sensitivity.

Cell Biology↗

bioRxiv2025

Novel clonal lineages of wheat stem rust in the Southern Cone of South America

Puccinia graminis f. sp. tritici (Pgt) causes wheat stem rust, a devastating disease of cereals. Recent approaches to examine populations at a genomic level have provided valuable information on the genotypic diversity of Pgt populations in Africa, Europe and North America and evolutionary mechanisms underlying the emergence of new races. However, an in-depth characterisation of Pgt populations in South America has been lacking. To bridge this knowledge gap, 91 Pgt isolates were collected from Argentina and Uruguay in 2020 and 2021 and used to generate transcriptome and whole genome sequence data and pathotype information. Phylogenetic analyses revealed that this South American Pgt population includes three clonal lineages, two of which have not been detected elsewhere. The third lineage is globally dispersed, including isolates from Africa and the Middle East. The predominant lineage, unique to South America, encompassed 90% of the samples and showed related pathotypes differing by virulence on single resistance genes consistent with evolution by stepwise mutation within the clonal lineage. There was no evidence of sexual recombination giving rise to new genetic diversity in this population. These observations urge to routinely incorporate and compare genotypic data from South American Pgt isolates to surveillance data from other geographic regions.

evolutionary biology↗

bioRxiv2025

Tracking community change via network coherence

Understanding how ecological communities respond to environmental change remains a key challenge for biodiversity monitoring. To characterize such responses, we need tools that capture how coherently species respond across a community, and to predict their consequences, we must account for ecological interactions. We first introduce the Ecological Coherence (EC) framework, which describes how species co-responses are structured within a community. Building on this foundation, we extend it to Ecological Network Coherence (ENC), which embeds co-responses within the network of interactions by restricting them to interacting species. Both are expressed through two complementary representations: a response correlation matrix and the distribution of its values. The first can reveal aspects such as coherent or incoherent modules and the roles species play in shaping coherence, whereas the second provides a profile whose shape may serve as an early-warning indicator of instability. These can be applied to both intrinsic responses (environmental performance) and realized responses (abundance dynamics), derived from currently available monitoring data. We illustrate this approach in two empirical systems: a tropical pollination network, where interacting mutualists were more coherent in their temperature responses than the broader community, and a marine food web, where coherence in abundance trends shifted during collapse. Using a Lotka-Volterra model, we further show that ENC distributions with higher variance--reflecting stronger positive and negative co-responses--increase the risk of instability or amplification in dynamics. We also find that species influential in both the correlation matrix and the interaction matrix are key drivers of major dynamic shifts. These results point to the importance of further exploring ENC distributions as potential early-warning indicators of ecological disruption.

ecology↗

bioRxiv2025

Long-term surveillance suggests multiple hybridization events by nuclear reassortment and accelerated intercontinental spread of wheat yellow rust

O_LIEvolutionary forces affecting crop pathogens, including hybridization and long-distance dispersal (LDD), may have strong implications for food security and sustainable plant disease control at global scales. However, consolidated evidence is often lacking due to absence of consistent pathogen surveys beyond national capacities. C_LIO_LIOur study documents world-wide connectivity between populations of Puccinia striiformis, causing yellow rust on cereals and grasses, when analysing 3240 pathogen samples collected in 41 countries on six continents from 2009-2023. Our analyses revealed twelve cases of inter-continental spread of Puccinia striiformis, including seven cases with major impact on disease epidemics in recipient areas. C_LIO_LISomatic hybridization by nuclear reassortment between co-existing multi-locus genotypes (MLGs) on a common host was the most plausible mechanism for the emergence of three novel clonal groups of global relevance, first detected in Europe. Subsequently, onwards spread to South America and Australia was observed. Several high-impact incursions from South Asia into East Africa were also observed, including a genotype with a dramatic impact on wheat breeding programs of global relevance. C_LIO_LIOur study stresses an urgent need for coordinated crop pathogens monitoring across borders. Only global efforts will enable prevention and control of pathogens that represent major challenges for food security at regional and global scales. C_LI

evolutionary biology↗

bioRxiv2025

Structure-based analysis unveils co-origin of LPOR and nitrogenase-like proteins

Structures of nitrogenases, dark-operative protochlorophyllide oxidoreductases, and light-dependent protochlorophyllide oxidoreductases (LPOR) have been resolved. However, their evolutionary relatedness remains elusive. Here, we show, through structural alignment, that all subunits of nitrogenase-like proteins originated from a co-ancestral archaic one-subdomain precursor. LPOR evolved from the BchX/BchY subunits of nitrogenase-like chlorophyllide a oxidoreductase (COR), and the intermediary retinol dehydrogenase through possible genetic recombination. We thus establish previously unknown structural links among key enzymes involved in biological nitrogen-fixation (BNF) and photosynthesis, unraveling structure-guided functional evolution from a single-subunit iron protein to multi-subunit nitrogenase-like COR, and to the single-subunit LPOR for phototrophic metabolism via bacteriochlorophyll, retinal, and chlorophyll. This work also demonstrates structural similarities are imperative for inferring distant origins of functionally divergent proteins, particularly those lacking primary amino-acid sequence identity. Moreover, our findings coupled with AI may be exploited to design innovative light-driven CORs and/or light-utilizing nitrogenases with enhanced efficacy of photosynthesis and BNF. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/634645v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@9f9a2aorg.highwire.dtl.DTLVardef@4243ecorg.highwire.dtl.DTLVardef@796b4corg.highwire.dtl.DTLVardef@17373da_HPS_FORMAT_FIGEXP M_FIG C_FIG Video abstracthttps://www.youtube.com/watch?v=b0qBE1JMaH0 HighlightsO_LILPOR evolves from BchX and BchY subunits of the nitrogenase-like protein (NGLP) COR C_LIO_LIAll subunits of NGLPs can be traced back to the ancestral one-subdomain precursor C_LIO_LIRetinol dehydrogenase acts as a crucial intermediate in the COR to LPOR evolution C_LIO_LIStructure-based design of LUN is showcased to revolutionize protein engineering C_LI

evolutionary biology↗

bioRxiv2025

Circadian Rhythms are Disrupted in Patients and Preclinical Models of Machado-Joseph Disease

Machado-Joseph disease (MJD) is caused by an abnormal CAG repeat expansion in the ATXN3 gene, leading to the expression of a mutant ataxin-3 (mutATXN3) protein. MJD patients exhibit a wide range of clinical symptoms, including motor incoordination. Emerging evidence highlights circadian rhythm disruptions as early indicators and potential risk factors for the progression of neurodegenerative conditions. Circadian rhythms are regulated by internal clocks, with the suprachiasmatic nucleus (SCN) acting as the master pacemaker to synchronize timing across the bodys behavioural and physiological functions. While sleep disturbances have been observed in MJD, the role of clock regulation in its pathophysiology remains largely unexplored in spinocerebellar ataxias. This study aimed to investigate circadian rhythms, characterize associated disruptions, and uncover the mechanisms underlying clock dysregulation in patients and preclinical models of MJD. Circadian activity in MJD patients was assessed over two weeks using actigraphy, while in a YAC-MJD transgenic mouse model, circadian rhythms were examined through: (a) wheel-running experiments; (b) telemetry-based monitoring of core body temperature; (c) immunohistochemical analysis of the neuropeptides arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in the SCN and paraventricular nucleus (PVN); and (d) RT-qPCR evaluation of clock gene expression in the cerebellum. The impact of mutATXN3 on clock mechanisms was further investigated using Bmal1/Per2-luciferase reporters. MJD patients exhibited a progressive decline in robustness of behavioural rhythms, demonstrated by negative correlations between the circadian function index, rest-activity fragmentation, and sleep efficiency with MJD clinical scales. YAC-MJD mice exhibited reduced activity levels, increased behavioural fragmentation, and required three additional days to re-entrain after a jet lag protocol, compared to controls. Disrupted core body temperature rhythms were observed, including a phase advance and elevated temperature ([~]1 {degrees}C) at the onset of the active period. Furthermore, transgenic mice showed reduced levels of VIP and AVP in the SCN and PVN, and decreased clock gene expression in the cerebellum. Lastly, we found new mechanistic evidence that WT ATXN3 activates the promoters of Bmal1 and Per2, whereas mutATXN3 loses the capacity to drive Per2 upon polyglutamine expansion. Overall, our findings indicate that central clock dysfunction in MJD is associated with impaired clock gene expression and disruptions in activity and temperature rhythms. This study provides the first robust evidence of circadian rhythm dysregulation and underlying mechanisms in MJD, paving the way for the identification of new biomarkers and the development of novel circadian-based interventions to tackle MJD and possibly other spinocerebellar ataxias. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/631212v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@25078dorg.highwire.dtl.DTLVardef@112e523org.highwire.dtl.DTLVardef@1818356org.highwire.dtl.DTLVardef@1d5a6c0_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Small form factor implantable neural probe with efficient flip chip micro LED for in vivo optogenetics

Optogenetics is a widely used tool to dissect neural circuits with optical stimulation, but it requires that light is delivered to photosensitive neurons inside the brain. Implantable neural probes with microscale LEDs (LEDs) are an emerging approach to delivering light to the brain with superior light output control. However, approaches to integrate LEDs in neural probes depend on complex fabrication processes. Here, we developed an implantable small form factor neural probe that integrates highly efficient commercial flip chip LEDs using only standard lithography processes in silicon and a custom automated LED mounting approach with custom 3D-printed tools on a pick-and-place machine. The probe has a cross-sectional area under 0.013 mm2 but can output up to 2.5 mW of optical power with an irradiance of 175 mW/mm2. Due to the high plug efficiency of the LED, the neural probe can perform stimulation protocols up to 20 Hz and 80% duty cycles without surpassing estimated hotspot temperature elevations above 1 {o}C. The neural probes were validated in vivo, with brain activity in the motor cortex of transgenic mice being reliably modulated by pulsed light emitted from the probe.

bioengineering↗

bioRxiv2024

Molecular control of dormancy transitions throughout the year in the monoecious cork oak

Bud dormancy plays a vital role in flowering regulation and fruit production, being highly regulated by endogenous and environmental cues. Deployment of epigenetic modifications and differential gene expression control bud dormancy/break cycles. Information on how these genetic and epigenetic mechanisms are regulated throughout the year is still scarce for temperate trees, such as Quercus suber. Here, the expression levels of QsCENL and QsDYL1 during different seasonal cycles of bud development suggest that QsCENL may be implicated in the establishment of growth cessation in Q. suber and that QsDYL1 is a good dormancy marker. Moreover, the analysis of the profiles of epigenetic marks and the expression of modifiers, in dormant versus non-dormant bud meristems, indicate that epigenetic regulation is implicated in how bud development progresses in Q. suber. The identification of bud specific mechanisms opens new possibilities to understand how trees respond to challenging environmental signals derived from climate change.

plant biology↗

bioRxiv2024

Tumor-derived hypoxic small extracellular vesicles promote endothelial cell migration and tube formation via ALS2/Rab5/β-catenin signaling

Tumor hypoxia has been associated with cancer progression, angiogenesis, and metastasis via modifications in the release and cargo composition of extracellular vesicles secreted by tumor cells. Indeed, hypoxic extracellular vesicles are known to trigger a variety of angiogenic responses via different mechanisms. We recently showed that hypoxia promotes endosomal signaling in tumor cells via HIF-1-dependent induction of the guanine exchange factor ALS2, which activates Rab5, leading to downstream events involved in cell migration and invasion. Since Rab5-dependent signaling is required for endothelial cell migration and angiogenesis, we explored the possibility that hypoxia promotes the release of small extracellular vesicles containing ALS2, which in turn activate Rab5 in recipient endothelial cells leading to pro-angiogenic properties. In doing so, we found that hypoxia promoted ALS2 expression and incorporation as cargo within small extracellular vesicles, leading to subsequent transfer to recipient endothelial cells, promoting cell migration, tube formation and downstream Rab5 activation. Consequently, ALS2-containing small extracellular vesicles increased early endosome size and number in recipient endothelial cells, which was followed by subsequent sequestration of components of the {beta}-catenin destruction complex within endosomal compartments, leading to stabilization and nuclear localization of {beta}-catenin. These events converged in the expression of {beta}-catenin target genes involved in angiogenesis. Knockdown of ALS2 in donor-tumor cells, which precluded its incorporation into small extracellular vesicles, prevented Rab5-downstream events and endothelial cell responses, which depended on Rab5 activity and guanine exchange factor activity of ALS2. These findings indicate that vesicular ALS2, secreted in hypoxia, promotes endothelial cell events leading to angiogenesis. Finally, these events might explain how tumor angiogenesis proceeds in hypoxic conditions.

cell biology↗

bioRxiv2024

Small non-coding RNA content in plasma-derived extracellular vesicles distinguish ataxic SCA3 mutation carriers from pre-ataxic and control subjects

Spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disorder caused by a CAG expansion in the ATXN3 gene, is the most common spinocerebellar ataxia subtype worldwide. Currently, there is no therapy to stop or prevent disease progression. Promising therapeutic strategies are emerging, but their translation into clinical practice requires sensitive and reliable biomarkers. Blood circulating extracellular vesicles constitute a promising source of biomarkers with potential to track alterations of the central nervous system due to their ability to cross the blood brain barrier. Here, we perform sequencing analysis of small RNAs from plasma-derived extracellular vesicles from SCA3 mutation carriers (10 pre-ataxic and 10 ataxic) and 12 control subjects to identify potential RNA biomarker candidates for this disease. Data showed that plasma-derived extracellular vesicles from ataxic SCA3 mutation carriers are enriched in mitochondrial, nuclear, and nucleolar RNA biotypes compared to pre-ataxic and control subjects. Moreover, ataxic mutation carriers could be discriminated from control and pre-ataxic subjects based on the miRNAs or piRNAs content, but not tRNA. Furthermore, we identified a subset of differentially expressed miRNAs and piRNAs that clearly differentiate ataxic mutation carriers from pre-ataxic and control subjects. These findings open new avenues for further investigation on the role of these RNAs in the pathogenesis of SCA3 and their potential as biomarkers for this disease.

neuroscience↗

bioRxiv2023

New races with wider virulence indicate local evolution of Puccinia striiformis f. sp. tritici in South America

Wheat yellow (stripe) rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat worldwide. Pst populations are composed of multiple genetic groups, each carrying one or more races characterized by different avirulence/virulence combinations. Since the severe epidemics in 2017, yellow rust has become the most economically important wheat foliar disease in Uruguay. Evolution of virulence was investigated based on genotyping and race typing of a representative set of 27 Pst isolates collected from wheat fields in Uruguay between 2017 and 2021. Three genetic groups were identified, i.e., PstS7, PstS10 and PstS13, the latter being the most prevalent. Two races previously reported in Europe, Warrior (PstS7) and Benchmark (PstS10), were detected in four and two isolates, respectively. A third race known as Triticale2015 (PstS13), first detected in Europe in 2015 and in Argentina in 2017, was detected at several locations. Additional virulence to Yr3, Yr17, Yr25, Yr27 or Yr32 was detected in three new race variants within PstS13. The identification of these new races, which have not been reported outside South America, provides strong evidence of the local evolution of virulence in Pst during the recent epidemic years.

pathology↗

bioRxiv2022

Applied phenomics and genomics for improving barley yellow dwarf resistance in winter wheat

Barley yellow dwarf (BYD) is one of the major viral diseases of cereals. Phenotyping BYD in wheat is extremely challenging due to similarities to other biotic and abiotic stresses. Breeding for resistance is additionally challenging as the wheat primary germplasm pool lacks genetic resistance, with most of the few resistance genes named to date originating from a wild relative species. The objectives of this study were to, i) evaluate the use of high-throughput phenotyping (HTP) from unmanned aerial systems to improve BYD assessment and selection, ii) identify genomic regions associated with BYD resistance, and iii) evaluate genomic prediction models ability to predict BYD resistance. Up to 107 wheat lines were phenotyped during each of five field seasons under both insecticide treated and untreated plots. Across all seasons, BYD severity was lower with the insecticide treatment and plant height (PTHTM) and grain yield (GY) showed increased values relative to untreated entries. Only 9.2% of the lines were positive for the presence of the translocated segment carrying resistance gene Bdv2 on chromosome 7DL. Despite the low frequency, this region was identified through association mapping. Furthermore, we mapped a potentially novel genomic region for resistance on chromosome 5AS. Given the variable heritability of the trait (0.211 - 0.806), we obtained relatively good predictive ability for BYD severity ranging between 0.06 - 0.26. Including Bdv2 on the predictive model had a large effect for predicting BYD but almost no effect for PTHTM and GY. This study was the first attempt to characterize BYD using field-HTP and apply GS to predict the disease severity. These methods have the potential to improve BYD characterization and identifying new sources of resistance will be crucial for delivering BYD resistant germplasm.

genetics↗

bioRxiv2021

Evolution of the bread wheat D-subgenome and enriching it with diversity from Aegilops tauschii

Aegilops tauschii, the diploid wild progenitor of the D-subgenome of bread wheat, constitutes a reservoir of genetic diversity for improving bread wheat performance and environmental resilience. To better define and understand this diversity, we sequenced 242 Ae. tauschii accessions and compared them to the wheat D-subgenome. We characterized a rare, geographically-restricted lineage of Ae. tauschii and discovered that it contributed to the wheat D-subgenome, thereby elucidating the origin of bread wheat from at least two independent hybridizations. We then used k-mer-based association mapping to identify discrete genomic regions with candidate genes for disease and pest resistance and demonstrated their functional transfer into wheat by transgenesis and wide crossing, including the generation of a library of synthetic hexaploids incorporating diverse Ae. tauschii genomes. This pipeline permits rapid trait discovery in the diploid ancestor through to functional genetic validation in a hexaploid background amenable to breeding.

plant biology↗

bioRxiv2019

The wild species genome ancestry of domestic chickens

Hybridization and/or introgression play a key role in the evolutionary history of animal species. It is commonly observed in several orders in wild birds. The domestic chicken Gallus gallus domesticus is the commonest livestock species exploited for the benefit of mankind. The origin of its diversity remains unsettled. Here, we report a genome-wide analyses for signatures of introgression within domestic village chicken. We first established the genome-wide phylogeny and divergence time across the genus Gallus, showing the sister relationships between Grey junglefowl G. sonneratii and Ceylon junglefowl G. lafayettii and that the Green junglefowl is the first diverging lineage within the genus Gallus. Then, by analysing the whole-genome sequences of geographically diverse chicken populations, we reveal extensive bidirectional introgression between Grey junglefowl and domestic chicken and to a much less extent with Ceylon junglefowl. A single case of Green junglefowl G. varius introgression was identified. These introgressed regions include biological functions related to the control of gene expression. Our results show that while the Red junglefowl is the main ancestral species, introgressive hybridization episodes have impacted the genome and contributed to the diversity of domestic chicken, although likely at different level across its geographic range.

evolutionary biology↗

bioRxiv2018

Engineering bacteria for biogenic synthesis of chalcogenide nanomaterials

Microbes naturally build nanoscale structures, including structures assembled from inorganic materials. Here we combine the natural capabilities of microbes with engineered genetic control circuits to demonstrate the ability to control biological synthesis of chalcogenide nanomaterials in a heterologous host. We transferred reductase genes from both Shewanella sp. ANA-3 and Salmonella enterica serovar Typhimurium into an heterologous host (Escherichia coli) and examined the mechanisms that regulate the properties of biogenic nanomaterials. Expression of arsenic reductase genes and thiosulfate reductase genes in E. coli resulted in the synthesis of arsenic sulfide nanomaterials. In addition to processing the starting materials via redox enzymes, cellular components also nucleated the formation of arsenic sulfide nanomaterials. The shape of the nanomaterial was influenced by the bacterial culture, with the synthetic E. coli strain producing nanospheres and conditioned media or cultures of wild type Shewanella sp. producing nanofibers. The diameter of these nanofibers also depended on the biological context of synthesis. These results demonstrate the potential for biogenic synthesis of nanomaterials with controlled properties by combining the natural capabilities of wild microbes with the tools from synthetic biology.

bioengineering↗

bioRxiv2017

Sofosbuvir protects Zika virus-infected mice from mortality, preventing short- and long-term sequela

Zika virus (ZIKV) caused significant public health concern, because of its association with congenital malformations, neurological disorders in adults and, more recently, with deaths. Considering the necessity to mitigate the cases ZIKV-associated diseases, antiviral interventions against this virus are an urgent necessity. Sofosbuvir, a drug in clinical use against Hepatitis C Virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 x 107 PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90 % in different anatomical compartments, such as in blood plasma, spleen, kidney and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals, despite the aggressive virus challenge assayed and also prevented the acute neuromotor impairment triggered by the virus. On the long-term behavior analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results point out that sofosbuvir inhibits ZIKV replication in vivo, which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals.

microbiology↗