Biology subjects

Ferreri, L.

Publications and source records attributed to Ferreri, L..

7 recordsLinked to original sources

bioRxiv2024

Dispersal of influenza virus populations within the respiratory tract shapes their evolutionary potential

Viral infections are characterized by dispersal from an initial site to secondary locations within the host. How the resultant spatial heterogeneity shapes within-host genetic diversity and viral evolutionary pathways is poorly understood. Here we show that dispersal within and between the nasal cavity and trachea maintains diversity and is therefore conducive to adaptive evolution, whereas dispersal to the lungs is stochastic and gives rise to population heterogeneity. We infected ferrets either intranasally or by aerosol with a barcoded influenza A/California/07/2009 (H1N1) virus. At 1, 2 or 4 days post infection, dispersal was assessed by collecting 52 samples from throughout the respiratory tract of each animal. Irrespective of inoculation route, barcode compositions across the nasal turbinates and trachea were similar and highly diverse, revealing little constraint on the establishment of infection in the nasal cavity and descent through the trachea. By comparison, infection of the lungs produced genetically distinct viral populations. Lung populations were pauci-clonal, suggesting that each seeded location received relatively few viral genotypes. While aerosol inoculation gave distinct populations at every lung site sampled, within-host dispersal after intranasal inoculation produced larger patches, indicative of local expansion following seeding of the lungs. Throughout the respiratory tract, barcode diversity declined over time, but new diversity was generated through mutation. De novo variants were often unique to a given location, indicating that localized replication following dispersal resulted in population divergence. In summary, dispersal within the respiratory tract operates differently between regions and contributes to the potential for viral evolution to proceed independently in multiple within-host subpopulations.

microbiology↗

bioRxiv2023

Role of the prefrontal cortex in musical and verbal short-term memory: A functional near-infrared spectroscopy study

Auditory short-term memory (STM) is a key process in auditory cognition, with evidence for partly distinct networks subtending musical and verbal STM. The delayed matching-to-sample task (DMST) paradigm has been found suitable for comparing musical and verbal STM and for manipulating memory load. In this study, musical and verbal DMSTs were investigated with measures of activity in frontal areas with functional near-infrared spectroscopy (fNIRS): Experiment 1 compared musical and verbal DMSTs with a low-level perception task (that does not entail encoding, retention, or retrieval of information), to identify frontal regions involved in memory processes. Experiment 2 manipulated memory load for musical and verbal materials to uncover frontal brain regions showing parametric changes in activity with load and their potential differences between musical and verbal materials. A FIR model was used to deconvolute fNIRS signals across successive trials without making assumptions with respect to the shape of the hemodynamic response in a DMST. Results revealed the involvement of the dorso-lateral prefrontal cortex (dlPFC) and inferior frontal gyri (IFG), but not of the superior frontal gyri (SFG) in both experiments, in keeping with previously reported neuroimaging data (including fMRI). Experiment 2 demonstrated a parametric variation of activity with memory load in bilateral IFGs during the maintenance period, with opposite directions for musical and verbal materials. Activity in the IFGs increased with memory load for verbal sound sequences, in keeping with previous results with n-back tasks. The decreased activity with memory load observed with musical sequences is discussed in relation to previous research on auditory STM rehearsal strategies. This study highlights fNIRS as a promising tool for investigating musical and verbal STM not only for typical populations, but also for populations with developmental language disorders associated with functional alterations in auditory STM.

neuroscience↗

bioRxiv2023

Swine influenza A virus isolates containing the pandemic H1N1 origin matrix gene elicit greater disease in the murine model

Since the 1990s, endemic North American swine influenza A viruses (swFLUAV) contained an internal gene segment constellation referred to as the triple reassortment internal gene (TRIG) cassette. In 2009, the H1N1 pandemic (pdmH1N1) virus spilled back into swine, but did not become endemic. However, the pdmH1N1 did contribute the matrix gene segment (pdmM) to the swFLUAVs circulating in the pig population; which replaced the classical swine matrix gene (swM) found in the TRIG cassette, suggesting that the pdmM has a fitness benefit. Others have shown that swFLUAV containing the pdmM have greater neuraminidase activity and transmission efficiency compared to viruses containing the swM gene segment. We hypothesized that the matrix gene could also affect disease and utilized two infection models, resistant BALB/c and susceptible DBA/2 mice, to assess swFLUAV pathogenicity. We infected BALB/c and DBA/2 mice with a panel of H1 and H3 swFLUAVs containing the swM or pdmM gene and measured lung virus titers, morbidity, mortality, and lung histopathology. H1 influenza strains containing the pdmM gene caused greater morbidity and mortality in both resistant and susceptible murine strains, while H3 swFLUAVs caused no clinical disease. However, both H1 and H3 swFLUAVs containing the pdmM replicated to higher viral titers in the lungs and pdmM containing H1 viruses induced greater histological changes compared to swM H1 viruses. While the surface glycoproteins contribute to swFLUAV pathogenicity, and other genes also influence disease, these data suggest that the origin of the matrix gene also contributes to pathogenicity of swFLUAV viruses in mice.

microbiology↗

bioRxiv2023

Antigenic mapping of the hemagglutinin of the H9 subtype influenza A viruses using sera from Japanese quail (Coturnix c. japonica).

Influenza A viruses (FLUAV) of the H9N2 subtype are zoonotic pathogens that cause significant economic damage to the poultry industry. Vaccination to prevent and control H9N2 infections in poultry is widely employed in the Middle East and Asia. We used phylogenetics and antigenic analysis to study the antigenic properties of the H9 hemagglutinin (HA) using sera produced in Japanese quail (Coturnix c. japonica). Consensus HA1 sequences were generated to capture antigenic diversity among isolates. We constructed chimeric H9N2 viruses containing the HA1 of each consensus sequence on a constant isogenic backbone. The resulting viruses were used to generate antisera from quail, a common and significant minor poultry species whose anti-HA response profiles remain poorly defined. Antigenic maps were generated by plotting the cross-hemagglutination inhibition (HI) data from the panel of quail sera against the chimeric constructs and 51 H9 field isolates. The chimeric antigens were divided into four different antigenic profiles (cyan, blue, orange, and red). Site-directed mutagenesis analysis showed 9 amino acid positions of antigenic relevance. Substitutions at amino acid positions 149, 150, and 180 (H9 HA numbering) had relatively significant impact on HI activity using quail sera. Substitutions E180A and R131K/E180A led to the most significant antigenic change transitions. This study provides insights into the antigenic profile of H9 FLUAVs, with important implications for understanding antigenic drift and improving vaccine development for use in minor poultry species. IMPORTANCEDetermining the relevant amino acids involved in antigenic drift on the surface protein hemagglutinin (HA) is critical to understand influenza virus evolution and efficient assessment of vaccine strains relative to current circulating strains. We used antigenic cartography to generate an antigenic map of the H9 HA using sera produced in one of the most relevant minor poultry species, Japanese quail. Key antigenic positions were identified and tested to confirm their impact on the antigenic profile. This work provides a better understanding of the antigenic diversity of the H9 HA as it relates to reactivity to quail sera and will facilitate a rational approach for selecting more efficacious vaccines against poultry-origin H9 influenza viruses in minor poultry species.

microbiology↗

bioRxiv2022

Independent evolution of influenza A virus H1N1 in pigs in Guatemala

Commercial swine farms provide unique systems for interspecies transmission of influenza A viruses (FLUAVs) at the animal-human interface. Bidirectional transmission of FLUAVs between pigs and humans plays a significant role in the generation of novel strains that become established in the new host population. Active FLUAV surveillance was conducted for two years on a commercial pig farm in Southern Guatemala with no history of FLUAV vaccination. Nasal swabs (n=2,094) from fattening pigs (6 to 24 weeks old) with respiratory signs were collected from May 2016 to February 2018. Swabs were screened for FLUAV by RRT-PCR and full virus genomes of FLUAV-positive swabs were sequenced by next-generation sequencing (NGS). FLUAV prevalence was 12.0% (95% CI: 10.6% - 13.4%) with two distinct periods of high infection. All samples were identified as FLUAVs of the H1N1 subtype within the H1 swine clade 1A.3.3.2 and whose ancestors are the human origin 2009 H1N1 influenza pandemic virus (H1N1 pdm09). Compared to the prototypic reference segment sequence, 10 amino acid signatures were observed on relevant antigenic sites on the hemagglutinin. We also found that Guatemalan swine-origin FLUAVs show independent evolution from other H1N1 pdm09 FLUAVs circulating in Central America. The zoonotic risk of these viruses remains unknown, but strongly calls for continued FLUAV surveillance in pigs in Guatemala. ImportanceDespite increased surveillance efforts, the epidemiology of FLUAVs circulating in swine in Latin America remains understudied. For instance, the 2009 H1N1 influenza pandemic strain (H1N1 pdm09) emerged in Mexico, but its circulation remained undetected in pigs. In Central America, Guatemala is the country with the largest swine industry. We found a unique group of H1N1 pdm09 sequences that suggests independent evolution from similar viruses circulating in Central America. These viruses may represent the establishment of a novel genetic lineage with the potential to reassort with other co-circulating viruses, and whose zoonotic risk remains to be determined.

evolutionary biology↗

bioRxiv2020

Dopaminergic signalling modulates reward-driven music memory consolidation

Previously, we provided causal evidence for a dopamine-dependent effect of intrinsic reward on memory during self-regulated learning (Ripolles et al., 2016; Ripolles et al., 2018). Here, we further investigated the dopamine-dependent link between reward and memory by focusing on one of the most iconic abstract rewards in humans: music. Twenty-nine healthy participants listened to unfamiliar excerpts--which had to be remembered following a consolidation period--after the intake of a dopaminergic antagonist, a dopaminergic precursor, and a placebo across three separated sessions. The intervention modulated the pleasantness experienced during music-listening and memory recognition of the presented songs (i.e., lower with the antagonist, higher with the precursor) in individuals with higher sensitivity to musical reward. Our work highlights the flexibility of the human dopaminergic system, which is able to enhance memory formation not only through explicit and/or primary reinforcers but also via intrinsic, abstract, or aesthetic rewards of different natures.

neuroscience↗

bioRxiv2018

Intrinsically regulated learning is modulated by synaptic dopamine availability

We recently provided evidence that an intrinsic reward-related signal--triggered by successful learning in absence of any external feedback--modulated the entrance of new information into long-term memory via the activation of the dopaminergic midbrain, hippocampus, and ventral striatum (the SN/VTA-Hippocampal loop; Ripolles et al., 2016). Here, we used a double-blind, within-subject randomized pharmacological intervention to test whether this learning process is indeed dopamine-dependent. A group of healthy individuals completed three behavioural sessions of our learning task after the intake of different pharmacological treatments: a dopaminergic precursor, a dopamine receptor antagonist or a placebo. Results show that the pharmacological intervention bidirectionally modulated behavioral measures of both learning and pleasantness, inducing memory benefits after 24 hours only for those participants with a high sensitivity to reward. These results provide causal evidence for a dopamine-dependent mechanism instrumental in intrinsically regulated learning, and further suggest that subject-specific dopamine sensitivity drastically alters learning success.

neuroscience↗