Biology subjects
Publications and source records attributed to Francois, S..
We report the complete CDS of five viruses: an iflavirus, a protoambidensovirus and three microviruses),which were detected by viromics surveillance of mosquitoes (Aedes albopictus and Culex quinquefasciatus) from the Reunion Island. We detected the protoambidensovirus, which belongs to aclade previously reported only in C. pipiens, in A. albopictus.
The effectiveness of vaccinating poultry in preventing the transmission of highly pathogenic avian influenza viruses (AIVs) has been questioned for years and its impact on wild birds is uncertain 1-3. Here we reconstruct movements of H5 subtype AIV lineages among vaccinated poultry, unvaccinated poultry, and wild birds, worldwide from 1996 to 2023. We find that lineage transitions among host types are lagged and that movements from wild birds to unvaccinated poultry were more frequent than those from wild birds to vaccinated poultry. However, we also find that the HA gene of the AIV lineage that circulated predominately among Chinese poultry with high vaccination coverage underwent faster evolution and greater nonsynonymous divergence than other lineages. Further, this Chinese poultry lineage contained more codons inferred to be under positive selection, including at known antigenic sites, and its rates of nonsynonymous divergence and adaptative fixation increased after mass poultry vaccination began. Our results indicate that the epidemiological, ecological and evolutionary consequences of widespread AIV vaccination in poultry may be linked in complex ways, and that much work is needed to better understand how such interventions may affect AIV transmission to, within and from wild birds.
During viral infections, type I interferons (IFN) are induced and play a key role in counteracting initial viral spread. Twelve different human IFN subtypes exist that bind the same receptor; however, they elicit unique host responses and display distinct potencies of antiviral activities. Our previous studies on HIV and HBV demonstrated that the clinically used IFN2 is not the most effective one among the IFN subtypes. By sequence modeling, we identified a region in helix B with mainly conserved residues at the outside facing IFNAR1, but variable residues at the inside facing the core of IFN, potentially representing a putative tunable anchor to tune pleiotropic IFN responses. Using site-directed mutagenesis various mutations were introduced into the IFN2b backbone targeting sites which are important for binding to IFNAR1 and IFNAR2, the putative tunable anchor, or outside these three regions. Selected mutations were based on sequence differences to high antiviral subtypes IFN6 and IFN14. Treatment assays against HBV and HIV identified several critical residues for the antiviral activity of IFN mainly in the IFNAR1 binding region. Combined mutations of the IFN2 IFNAR1/2 binding sites or the IFNAR1 binding region plus the putative tunable anchor by those of IFN14 further augmented activation of different downstream signaling cascades providing a molecular correlate for the enhanced antiviral activity. We describe here important functional residues within IFN subtype molecules, which enabled us to design novel and innovative drugs that may have the potential to be used in clinical trials against a variety of different viral infections. ImportanceThe potency of IFN to restrict viruses was already discovered in 1957. However, until today only IFN2 out of the 12 distinct human IFN subtypes has been therapeutically used against chronic viral infections. There is convincing evidence that other IFN subtypes are far more efficient than IFN2 against many viruses. In order to identify critical antiviral residues within the IFN subtype sequence, we designed hybrid molecules based on the IFN2 backbone with individual sequence motifs from the more potent subtypes IFN6 and IFN14. In different antiviral assays with HIV or HBV, residues binding to IFNAR1 as well as combinations of residues in the IFNAR1 binding region, the putative tunable anchor, and residues outside these regions were identified to be crucial for the antiviral activity of IFN. Thus, we designed artificial IFN molecules, based on the clinically approved IFN2 backbone, but with highly improved antiviral activity against several viruses.
2.Viruses emerging from wildlife can cause outbreaks in humans and domesticated animals. Predicting the emergence of future pathogens and mitigating their impacts requires an understanding of what shapes virus diversity and dynamics in wildlife reservoirs. In order to better understand coronavirus ecology in wild species, we sampled birds within a coastal freshwater lagoon habitat across five years, focussing on a large population of mute swans (Cygnus olor) and the diverse species that they interact with. We discovered and characterised the full genome of a divergent gammacoronavirus belonging to the Goose coronavirus CB17 species. We investigated the genetic diversity and dynamics of this gammacoronavirus using untargeted metagenomic sequencing of 223 fecal samples from swans of known age and sex, and RT-PCR screening of 1632 additional bird samples. The virus circulated persistently within the bird community; virus prevalence in mute swans exhibited seasonal variations, but did not change with swan age-class or epidemiological year. One whole genome was fully characterised, and revealed that the virus originated from a recombination event involving an undescribed gammacoronavirus species. Multiple lineages of this gammacoronavirus co-circulated within our study population. Viruses from this species have recently been detected in aquatic birds from both the Anatidae and Rallidae families, implying that host species habitat sharing may be important in shaping virus host range. As the host range of the Goose coronavirus CB17 species is not limited to geese, we propose that this species name should be updated to "Waterbird gammacoronavirus 1". Non-invasive sampling of bird coronaviruses may provide a tractable model system for understanding the evolutionary and cross-species dynamics of coronaviruses.
Viral discovery studies in wild animals often rely on cross-sectional surveys at a single time point. As a result, our understanding of the temporal stability of wild animal viromes remains poorly resolved. While studies of single host-virus systems indicate that host and environmental factors influence seasonal virus transmission dynamics, comparable insights for whole viral communities in multiple hosts are lacking. Leveraging non-invasive faecal samples from a long-term wild rodent study, we characterised viral communities of three common European rodent species (Apodemus sylvaticus, A. flavicollis, and M. glareolus) living in temperate woodland over a single year. Our findings indicate that a substantial fraction of the rodent virome is seasonally transient and associated with vertebrate or bacteria hosts. Further analyses of one of the most abundant virus families, Picornaviruses, show pronounced temporal changes in viral richness and diversity, which were associated with concurrent and up to [~]3-month lags in host density, ambient temperature, rainfall and humidity, suggesting complex feedbacks from the host and environmental factors on virus transmission and shedding in seasonal habitats. Overall, this study emphasizes the importance of understanding the seasonal dynamics of wild animal viromes in order to better predict and mitigate zoonotic risks.
Herpesvirus infections are common and mostly asymptomatic in vertebrates, but can result in impaired reproduction. It is therefore important to understand infection patterns and associated risk factors, particularly the effects of different stressors. Here we use Mustelid gammaherpesvirus 1 (MusGHV-1) infection in European badgers (Meles meles) as a host-pathogen wildlife model to study the effects of a variety of demographic, social, physiological and environmental stressors on viral reactivation in the genital tract. We collected 251 genital swabs from 151 free-ranging individuals across 3 trapping seasons (spring, summer and autumn). We screened for MusGHV-1 using PCR and explored possible links between genital MusGHV-1 reactivation and stressors, and their interactions, using logistic regression. In adults, reactivation was more likely in males, especially those in poorer body condition during summer. In females, reactivation was more likely when living in social groups comprising a higher percentage of cubs, but counter to our predictions, recent lactation appeared not influential. In relation to age, reactivation was more common in individuals over 8 years old than among prime age adults, and among juveniles (<2 years old), especially females and individuals in better body condition, likely due to early puberty. Environmentally, reactivation was more prevalent in summer when food abundance is typically low. Our results evidence age effects on MusGHV-1 reactivation; in juveniles MusGHV-1 shedding in the genital tract is likely related to primary infection, while in adults, genital MusGHV-1 reactivation from latency was associated with aging, social and/ or environmental stress. ImportanceThe immuno-suppressive effects of elevated stress levels facilitate disease development, and can ultimately cause host extinction at the population level, especially where diseases are transmitted sexually. The impacts of stress on host-pathogen dynamics through disease, however, are still poorly understood outside the laboratory or captive environments. Our study provides rare evidence from a free-ranging wild mammal population that the infection dynamics of a common and sexually transmittable gammaherpesvirus are linked to demographic, social, physiological and environmental stress. We propose that the effects of stressors on STIs and viral reactivation are an important factor to be taken into account in conservation efforts when working with vulnerable wildlife populations.
The innate immune response induced by type I interferons (IFNs) play a critical role in the establishment of HIV infection. IFNs are induced early in HIV infection and trigger an antiviral defense program by signaling through the IFNa/b receptor (IFNAR), which consists of two subunits, IFNAR1 and IFNAR2. Changes in IFNAR expression in HIV target cells, as well as other immune cells, could therefore have important consequences for initial HIV spread. It was previously reported that IFNAR2 expression is increased in peripheral blood CD4+ CXCR4+ T cells of HIV+ patients compared to HIV uninfected controls, suggesting that HIV infection may alter the IFN responsiveness of target cells. However, the earliest immune cells affected by HIV in vivo reside in the gut-associated lymphoid tissue (GALT). To date, it remains unknown if IFNAR expression is altered in GALT immune cells in the context of HIV infection and exposure to IFNs, including the 12 IFNa subtypes. Here, we analyzed the expression of surface bound and soluble IFNAR2 on Lamina propria mononuclear cells (LPMCs) isolated from the GALT of HIV- individuals and in plasma samples of HIV+ patients. IFNAR2 expression varied between different T cells, B cells and natural killer cells, but was not altered following HIV infection. Furthermore, expression of the soluble IFNAR2a isoform was not changed in HIV+ patients compared to healthy donors, nor in LPMCs after HIV-1 infection ex vivo. Even though the 12 human IFN subtypes trigger different biological responses and vary in their affinity to both receptor subunits, stimulation of LPMCs with different recombinant IFN subtypes did not result in any significant changes in IFNAR2 surface expression. Our data suggests that potential changes in the IFN responsiveness of mucosal immune cells during HIV infection is unlikely dictated by changes in IFNAR2 expression.
We describe a global optimization approach for genome assembly where the steps of scaffolding, gap-filling, and scaffold extension are simultaneously solved in the framework of a common objective function. The approach is based on integer programming model for solving genome scaffolding as a problem of finding a long simple path in a specific graph that satisfies additional constraints encoding the insert-size information. The optimal solution of this problem allows one to obtain new kind of contigs that we call distance-based contig. We test the algorithm on a benchmark of chloroplasts and compare the quality of the results with recent scaffolders.