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Savini, G.

Publications and source records attributed to Savini, G..

6 recordsLinked to original sources
bioRxiv2025

How an arthropod-borne virus manages host switches: exploration of host-specific mutations and gene formula in bluetongue virus

Arthropod-borne viruses, also known as arboviruses, cause disease worldwide. These viruses alternate between vertebrates and arthropods, facing distinct selection pressures in each host type. Surprisingly, whether specific mechanisms facilitate host alternation remains unclear. Here, we use bluetongue virus (BTV) as a model to investigate two phenomena potentially facilitating host alternation: adaptive mutations and genome formula variation (GFV). First, we searched for mutations indicative of host adaptation in cattle, sheep, and midges infected during an epizooty. We found a limited number of parallel mutations. This result suggests that adaptive mutations are not a main mechanism facilitating host alternation in BTV. Second, we investigated a link of GFV with a proxy of viral fitness, the speed of virus dissemination in midges. We analyzed the genome formula (GF) in experimentally-infected Culicoides imicola midges, either with an infection disseminated into the head or not. GFs differed between dissemination levels, suggesting a link between GF and the speed of virus dissemination. Finally, we investigated the mechanisms underlying GF generation. Currently, two scenarios have been proposed: random generation followed by selection, or directed generation through molecular mechanisms. To limit the influence of selection, we analyzed the GF after a single replication cycle in cell culture. GF values converged towards specific values among replicates. Moreover, GFs differed between arthropod and vertebrate cells. Thus, GF generation is not purely stochastic and is probably influenced by host-specific mechanisms. Overall, our findings highlight GFV as a potential mechanism facilitating BTV alternation across hosts, but not classical mutation-driven evolution. Author SummaryArthropod-borne viruses are important public health problems in the world. These viruses follow a complex cycle involving alternation between arthropods and vertebrates. Surprisingly, we know little on the mechanisms that facilitate alternation between the two host types. Knowledge on such mechanisms could allow the development of antiviral tools. Here, using Bluetongue virus as a model, we investigated two potential mechanisms facilitating alternation: adaptive mutations and genome formula variation (GFV). We found limited evidence for host-specific mutations in natural populations. We observed a potential link between GFV and viral fitness. Moreover, our results suggest that molecular mechanisms generate GFV in a host-specific way from the first round of cell infection.

microbiology↗
bioRxiv2022

West Nile virus and Usutu virus in wild birds from Rescue Centers, a post-mortem monitoring study from Central Italy.

West Nile virus (WNV) and Usutu virus (USUV) are mosquito-borne flaviviruses causing world-wide numerous cases in animals and humans. In Italy, both viruses have been associated with neurological diseases in humans and wild birds. Wild bird rescue centers where support in emergency and care of diseased animals are provided, are potential significant hot spots for avian infection surveillance, as recognized in the Italian Integrate National Surveillance Plan for Arboviruses. Here we report the results of a post-mortem active monitoring study conducted from November 2017 to October 2020 on animals hosted in five wild bird rescue centers of Central Italy. Five hundred seventy-six (n = 576) wild birds were tested by real-time polymerase chain reaction (RT-PCR) for the presence of WNV or USUV RNA fragments. No birds tested positive for USUV RNA (n = 0; 0.00 %). Evidence of WNV RNA (Ct value = 34.36) was found in one bird (n = 1; 0.17 %), an adult little grebe (Tachybaptus ruficollis subsp. ruficollis), that tested WNV positive on December 2019 and died due to traumatic injuries. The main pathological findings consisted in mild CD3+ lymphocytic tubulo-interstitial nephritis, meningoencephalitis, and cardiomyocytes loss and interstitial oedema of the heart. This study highlights the strategic role of wildlife rescue centers in monitoring both the introduction and circulation of avian emerging zoonotic diseases. Also, the presence of WNV during the cold season evidences the possible role of birds in overwintering mechanisms in the Italian territory and requires further investigations.

microbiology↗
bioRxiv2019

Evolutionary stasis of an RNA virus indicates arbovirus re-emergence triggered by accidental release

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an insect-borne virus of ruminants, emerged in livestock in Northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of Euros. Though the outbreak was successfully controlled through vaccination by early 2010, puzzlingly a closely-related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this period without replication, we conclude that the second outbreak was most likely initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.

evolutionary biology↗
bioRxiv2019

The Glossina Genome Cluster: Comparative Genomic Analysis of the Vectors of African Trypanosomes

BackgroundTsetse flies (Glossina sp.) are the sole vectors of human and animal trypanosomiasis throughout sub-Saharan Africa. Tsetse are distinguished from other Diptera by unique adaptations, including lactation and the birthing of live young (obligate viviparity), a vertebrate blood specific diet by both sexes and obligate bacterial symbiosis. This work describes comparative analysis of six Glossina genomes representing three sub-genera: Morsitans (G. morsitans morsitans (G.m. morsitans), G. pallidipes, G. austeni), Palpalis (G. palpalis, G. fuscipes) and Fusca (G. brevipalpis) which represent different habitats, host preferences and vectorial capacity. ResultsGenomic analyses validate established evolutionary relationships and sub-genera. Syntenic analysis of Glossina relative to Drosophila melanogaster shows reduced structural conservation across the sex-linked X chromosome. Sex linked scaffolds show increased rates of female specific gene expression and lower evolutionary rates relative to autosome associated genes. Tsetse specific genes are enriched in protease, odorant binding and helicase activities. Lactation associated genes are conserved across all Glossina species while male seminal proteins are rapidly evolving. Olfactory and gustatory genes are reduced across the genus relative to other characterized insects. Vision associated Rhodopsin genes show conservation of motion detection/tracking functions and significant variance in the Rhodopsin detecting colors in the blue wavelength ranges. ConclusionsExpanded genomic discoveries reveal the genetics underlying Glossina biology and provide a rich body of knowledge for basic science and disease control. They also provide insight into the evolutionary biology underlying novel adaptations and are relevant to applied aspects of vector control such as trap design and discovery of novel pest and disease control strategies.

genomics↗
bioRxiv2018

Tractography Reproducibility Challenge with Empirical Data (TraCED): The 2017 ISMRM Diffusion Study Group Challenge

PurposeFiber tracking with diffusion weighted magnetic resonance imaging has become an essential tool for estimating in vivo brain white matter architecture. Fiber tracking results are sensitive to the choice of processing method and tracking criteria. Phantom studies provide concrete quantitative comparisons of methods relative to absolute ground truths, yet do not capture variabilities because of in vivo physiological factors.\n\nMethodsTo date, a large-scale reproducibility analysis has not been performed for the assessment of the newest generation of tractography algorithms with in vivo data. Reproducibility does not assess the validity of a brain connection however it is still of critical importance because it describes the variability for an algorithm in group studies. The ISMRM 2017 TraCED challenge was created to fulfill the gap. The TraCED dataset consists of a single healthy volunteer scanned on two different scanners of the same manufacturer. The multi-shell acquisition included b-values of 1000, 2000 and 3000 s/mm2 with 20, 45 and 64 diffusion gradient directions per shell, respectively.\n\nResultsNine international groups submitted 46 tractography algorithm entries. The top five submissions had high ICC > 0.88. Reproducibility is high within these top 5 submissions when assessed across sessions or across scanners. However, it can be directly attributed to containment of smaller volume tracts in larger volume tracts. This holds true for the top five submissions where they are contained in a specific order. While most algorithms are contained in an ordering there are some outliers.\n\nConclusionThe different methods clearly result in fundamentally different tract structures at the more conservative specificity choices (i.e., volumetrically smaller tractograms). The data and challenge infrastructure remain available for continued analysis and provide a platform for comparison.

neuroscience↗