Biology subjects

Dorigatti, I.

Publications and source records attributed to Dorigatti, I..

9 recordsLinked to original sources

bioRxiv2026

West Nile virus response to mosquito and avian biodiversity in rural environments

ContextThe relationship between biodiversity and zoonotic disease risk is a central topic in community ecology, yet empirical evidence in Europe remains scarce and often contradictory compared to North American studies. Addressing this gap is fundamental to better anticipate zoonotic disease dynamics. ObjectivesWe investigated the transmission dynamics of West Nile virus (WNV) in Veneto (Italy), a major European hotspot. Because this vector-borne pathogen is primarily transmitted by Culex mosquitoes and maintained by several avian hosts, we analysed how multiple facets of both avian and mosquito biodiversity influence its transmission. MethodsUsing Generalized Additive Models (GAMs) trained on longitudinal entomological and ornithological surveillance data, we modelled the probability of WNV presence in mosquito pools as a function of host and vector community structure. To isolate the effects of biodiversity, we explicitly controlled for climatic and landscape covariates. ResultsIn agricultural landscapes, we found that higher avian diversity leads to higher viral presence, driven by the dominance of highly competent synanthropic hosts. Conversely, a dilution effect emerges across the broader regional landscape where areas of higher ecological integrity allow for more complex and functionally diverse avian communities. Furthermore, we identified significant vector-mediated regulation, where high abundances of mammophilic vectors effectively suppress viral prevalence through larval competition. ConclusionsOur findings suggest that the dilution effect is a property of intact ecosystems which can be lost, or even locally reversed, in anthropogenically altered environments. Because such habitat degradation fundamentally alters zoonotic transmission dynamics, landscape planning must prioritize ecological restoration. Ultimately, embedding these practices into One Health strategies represents a proactive approach to mitigating disease emergence.

ecology↗

bioRxiv2026

Beyond the surface: plasmalogens are dispensable for retinal integrity and fertility in the mouse

Ether lipids and their subclass, the plasmalogens, are critical regulators of membrane organization, signaling, and stress responses in multiple tissues. Inborn errors in their anabolism cause severe multi-organ diseases such as Rhizomelic Chondrodysplasia Punctata and related peroxisomal disorders. The Gnpat knockout mouse model, characterized by total ether lipid deficiency, recapitulates key features of this disorder, including dense bilateral cataracts, microphthalmia, and infertility, but the specific contribution of different subclasses like plasmalogens remains elusive. The recent identification of the Peds1 gene allows dissecting the impact of selective plasmalogen deficiency with retention of plasmanyl lipids, another ether lipid subgroup. Here, we performed the first side-by-side comparison of Gnpat and Peds1 knockout in mice on a matched genetic background (C57BL/6 x CD1). In contrast to the situation in Gnpat knockout mice, plasmanyl lipids in Peds1 knockout mice were sufficient to prevent cataract formation and maintain normal ocular structures, despite marked shifts in the ocular phospholipidome. Also, fertility and reproductive function were found to be preserved in Peds1 knockout mice. Our data demonstrate that plasmanyl lipids can partially protect against the severe phenotypes observed in mouse models of total ether lipid deficiency; notably, the ocular and reproductive phenotypes were plasmalogen-independent, indicating that loss of the vinyl ether double bond is not the key determinant of all symptoms in human and murine ether lipid deficiency and can at least partly be compensated by plasmanyl lipids. HighlightsO_LIIn mice, total ether lipid deficiency causes cataracts and infertility. C_LIO_LIThe role of plasmalogens in these phenomena remains unclear. C_LIO_LITwo PEDS1-deficient patients were reported, but cataracts were observed in only one case. C_LIO_LIPeds1-deficient mice have no cataracts or ocular abnormalities. C_LIO_LIMice with a deletion of Peds1 display normal fertility rates. C_LI

biochemistry↗

bioRxiv2026

Plasmalogen metabolism shapes germinal center immunity

Plasmalogens are membrane lipids whose roles in immunity are emerging through identification of the PEDS1 gene and advances in lipid analytics. Because PEDS1 catalyses the final step of plasmalogen biosynthesis, Peds1 knockout models plasmalogen loss. Building on reports of a haematopoietic phenotype in Peds1-deficient mice, we performed extended profiling to characterise haematological and immune phenotypes. In line with these previous investigations, mice showed reduced red blood cell counts and haematocrit, with increased mean platelet volume. At steady state, plasmalogen deficiency was associated with reduced germinal centre (GC) B cell frequencies in mucosal lymphoid tissues and lower basal serum IgG1 levels. Following immunisation, GC B cell frequencies and ovalbumin-specific IgG1 were similar across genotypes, yet GC B cells exhibited elevated mitochondrial superoxide and plasma cells displayed increased lipid peroxidation. To test for B cell-intrinsic effects, we used an in vitro GC culture, where Peds1-deficient B cells showed reduced class switching to IgG1, intracellular IgG1 accumulation and diminished IgG1 secretion. Together, these findings support a role for plasmalogens and PEDS1 as a lipid-metabolic modulator of GC dynamics and IgG1 output, consistent with broader ether lipid perturbations. Plasmalogen metabolism may therefore offer a potential entry point to modulate humoral immunity or haematopoiesis.

immunology↗

bioRxiv2025

Association of avian biodiversity and West Nile virus circulation in Culex mosquitoes in Emilia-Romagna, Italy

West Nile Virus (WNV) is a zoonotic arbovirus maintained in a transmission cycle between Culex mosquitoes and birds, occasionally spilling over into humans. The impact of avian biodiversity on WNV circulation remains debated, with studies reporting both negative and positive correlations (dilution and amplification effects respectively) across different settings. In Europe, this relationship remains largely unexplored, particularly in regions with high WNV transmission, such as Emilia-Romagna in Northern Italy. We explored the association between avian biodiversity and WNV circulation in Culex mosquitoes in Emilia-Romagna using 11 consecutive years (2013-2023) of entomological surveillance data paired with two avian data sources. We calculated avian biodiversity indices (Shannons, Simpsons, and Chao2) from observation records from the Farmland Bird Index project and applied linear regression models to assess their relationship with WNV circulation levels. Moreover, we used Bayesian spatiotemporal regression models and gridded weekly avian abundance estimates from the eBird project, to analyse the associations between avian species richness indices and WNV-positivity rates at 68 geolocated mosquito traps across the region. We observed consistent negative associations between WNV circulation in the Culex population and avian biodiversity indices, supporting the dilution effect hypothesis (DEH). We found that non-passerine species richness was negatively associated with WNV mosquito circulation, whereas passerine species richness exhibited a positive association after adjusting for environmental factors and spatial random effects. These findings suggest that passerines may amplify WNV transmission, while the presence of non-passerine species is associated with reductions in WNV circulation. This study provides the first empirical evidence supporting the DEH for WNV in Europe. These findings have important implications for avian surveillance and future WNV modelling studies, and can inform regional, national and European policies on biodiversity conservation and public health planning. Author summaryWest Nile Virus (WNV) is a zoonotic, vector-borne disease maintained in a mosquito-bird-mosquito transmission cycle. The role of avian biodiversity in WNV transmission remains debated, with studies reporting both dilution effects (negative associations) and amplification effects (positive associations) across different settings. Here, we examined the impact of avian biodiversity on WNV circulation in Culex mosquitoes in Emilia-Romagna, Italy, one of Europes WNV hotspots. We analysed 11 years (2013-2023) of entomological surveillance data alongside two ornithological datasets, respectively collected by the Farmland Bird Index project and the citizen science project eBird. These different datasets allowed us to test the dilution effect hypothesis (DEH) at broad and fine spatiotemporal resolutions. Our findings provide support for the DEH for WNV, revealing that higher bird community diversity is associated with reduced WNV circulation. Additionally, we found that non-passerine species richness is linked to lower levels of WNV circulation in the vector, whereas passerine species richness is positively associated with WNV transmission from entomological surveillance. These results point towards the potential amplifying role of passerine species and the protective role of non-passerine species in WNV transmission dynamics, which has important implications for species conservation, public health policy and future modelling studies.

ecology↗

bioRxiv2024

Predicting the infecting dengue serotype from antibody titre data using machine learning

The development of a safe and efficacious vaccine that provides immunity against all four dengue virus serotypes is a priority, and a significant challenge for vaccine development has been defining and measuring serotype-specific outcomes and correlates of protection. The plaque reduction neutralisation test (PRNT) is the gold standard assay for measuring serotype-specific antibodies, but this test cannot differentiate homotypic and heterotypic antibodies and characterising the infection history is challenging. To address this, we present an analysis of pre- and post-infection antibody titres measured using the PRNT, collected from a prospective cohort of Thai children. We applied four machine learning classifiers and multinomial logistic regression to the titre data to predict the infecting serotype. The models were validated against the true infecting serotype, identified using RT-PCR. Model performance was calculated using 100 bootstrap samples of the train and out-of-sample test sets. Our analysis showed that, on average, the greatest change in titre was against the infecting serotype. However, in 53.4% (109/204) of the subjects, the highest titre change did not correspond to the infecting serotype, including in 34.3% (12/35) of dengue-naive individuals. The highest post-infection titres of seropositive cases were more likely to match the serotype of the highest pre-infection titre than the infecting serotype, consistent with original antigenic sin. Despite these challenges, the best performing machine learning algorithm achieved 76.3% (95% CI 57.9-89.5%) accuracy on the out-of-sample test set in predicting the infecting serotype from PRNT data. Incorporating additional spatiotemporal data improved accuracy to 80.6% (95% CI 63.2-94.7%), while using only post-infection titres as predictor variables yielded an accuracy of 71.7% (95% CI 57.9-84.2%). These results show that machine learning classifiers can be used to overcome challenges in interpreting PRNT titres, making them useful tools in investigating dengue immune dynamics, infection history and identifying serotype-specific correlates of protection, which in turn can support the evaluation of clinical trial endpoints and vaccine development.

immunology↗

bioRxiv2023

Modelling the viral dynamics of the SARS-CoV-2 Delta and Omicron variants in different cell types

We use viral kinetic models fitted to viral load data from in vitro studies to explain why the SARS-CoV-2 Omicron variant replicates faster than the Delta variant in nasal cells, but slower than Delta in lung cells, which could explain Omicrons higher transmission potential and lower severity. We find that in both nasal and lung cells, viral infectivity is higher for Omicron but the virus production rate is higher for Delta. However, the differences are unequal between cell types, and ultimately leads to the basic reproduction number and growth rate being higher for Omicron in nasal cells, and higher for Delta in lung cells. In nasal cells, Omicron alone can enter via a TMPRSS2-independent pathway, but it is primarily increased efficiency of TMPRSS2-dependent entry which accounts for Omicrons increased activity. This work paves the way for using within-host mathematical models to understand the transmission potential and severity of future variants.

microbiology↗

bioRxiv2021

Rapid longitudinal SARS-CoV-2 intra-host emergence of novel haplotypes regardless of immune deficiencies

On February 2020, the municipality of Vo, a small town near Padua (Italy), was quarantined due to the first coronavirus disease 19 (COVID-19)-related death detected in Italy. The entire population was swab tested in two sequential surveys. Here we report the analysis of the viral genomes, which revealed that the unique ancestor haplotype introduced in Vo belongs to lineage B and, more specifically, to the subtype found at the end of January 2020 in two Chinese tourists visiting Rome and other Italian cities, carrying mutations G11083T and G26144T. The sequences, obtained for 87 samples, allowed us to investigate viral evolution while being transmitted within and across households and the effectiveness of the non-pharmaceutical interventions implemented in Vo. We report, for the first time, evidence that novel viral haplotypes can naturally arise intra-host within an interval as short as two weeks, in approximately 30% of the infected individuals, regardless of symptoms severity or immune system deficiencies. Moreover, both phylogenetic and minimum spanning network analyses converge on the hypothesis that the viral sequences evolved from a unique common ancestor haplotype, carried by an index case. The lockdown extinguished both viral spread and the emergence of new variants, confirming the efficiency of this containment strategy. The information gathered from household was used to reconstructs possible transmission events. AUTHOR SUMMARYIt is of great interest and importance to understand SARS-CoV-2 ability to mutate generating new viral strains, and to assess the impact of containment strategies on viral transmission. In this study we highlight the rapid intra-host haplotype evolution regardless of symptom severity and immune deficiencies that we observed during the first wave of the pandemic in the municipality of Vo in Italy. The confirmation that all the haplotypes found in this small community derive from a common ancestor haplotype, has allowed us to track the rapid emergence of new variants but lockdown and mass testing efficiently prevented their spread elsewhere.

evolutionary biology↗

bioRxiv2018

Spatiotemporal Variability in Dengue Transmission Intensity in Jakarta, Indonesia

BackgroundApproximately 70% of the global burden of dengue disease occurs on the Asian continent, where many large urban centres provide optimal environments for sustained endemic transmission and periodic epidemic cycles. Jakarta, the capital of Indonesia, is a densely populated megacity with hyperendemic dengue transmission. Characterization of the spatiotemporal distribution of dengue transmission intensity is of key importance for optimal implementation of novel control and prevention programmes, including vaccination. In this paper we use mathematical models to provide the first detailed description of spatial and temporal variability in dengue transmission in Jakarta.\n\nMethodology/Principal FindingsWe applied catalytic models in a Bayesian framework to age-stratified dengue case notification data to estimate dengue force of infection and reporting probabilities in 42 subdistricts of Jakarta. The model was fit to yearly and average annual data covering a 10- year period between 2008 and 2017. We estimated a long-term average annual transmission intensity of 13.0% (95%CrI: 12.9-13.1%) per year in Jakarta province, ranging from 9.0% (95%CrI: 7.7-10.3%) to 16.4% (95%CrI: 15.3-17.4%) across subdistricts. Annual average transmission intensity in Jakarta province during the 10-year period ranged from 1.2% (95%CrI: 1.1-1.3%) in 2017 to 12.4% (95%CrI: 12.1-12.8%) in 2016.\n\nConclusions/SignificanceWhile the absolute number of dengue case notifications cannot be relied upon as a measure of endemicity, the age-distribution of reported dengue cases provides valuable insights into the underlying nature of transmission. Our estimates from yearly and average annual case notification data represent the first detailed estimates of dengue transmission intensity in Jakartas subdistricts, which will be important to consider when assessing the population-level impact and cost-effectiveness of potential control and prevention programmes in Jakarta province, such as the controlled release of Wolbachia-carrying mosquitoes and vaccination.

epidemiology↗

bioRxiv2017

International risk of yellow fever spread from the ongoing outbreak in Brazil

The largest Yellow Fever (YF) outbreak in a decade in Latin America is underway in the Southeast of Brazil. In this article we provide a quantitative assessment of the risk of travel-related international spread of YF. We argue that mitigating the risk of imported YF cases seeding local transmission requires heightened surveillance in the southern United States, Latin America (especially Argentina, Chile and Uruguay) and Europe (especially Portugal, Spain, Italy and Germany).

epidemiology↗