Biology subjects

Gessain, A.

Publications and source records attributed to Gessain, A..

8 recordsLinked to original sources

bioRxiv2025

In vivo risk assessment of yellow fever virus transmission through breastfeeding, and mechanistic insights

Yellow fever virus (YFV), a mosquito-borne flavivirus, remains a significant public health threat, especially in areas with low vaccine coverage. Since 2010, yellowfevervaccination is not recommended for breastfeeding women due to reported cases of vaccine strain transmission through breast milk, leading to neonatal meningoencephalitis. However, the efficiency of YFV vaccine strain transmission via breastfeeding remains unknown, and wild-type strains transmission may be suspected based on viral RNA detection in breast milk. Direct evidence of breastfeeding-related transmission in humans is challenging to obtain given the confounding presence of vector-borne transmission, making animal models crucial for evaluating this risk. In this study, the A129 mouse model was used to investigate YFV transmission via breastfeeding for both wild-type and vaccine strains. Results show that both strains can spread to mammary glands, leading to viral detection in breast milk as free viral particles and cell-associated virus, with similar viral loads for all strains. Mammary stromal and immune cells are primary targets of YFV in vivo, while mammary epithelial cells also support infection, suggesting two possible mechanisms of mammary epithelial crossing. Neonates are found to be susceptible to oral infection, with higher infection rates for the wild-type strain but evidence of neuroinvasion for both strains. Both strains can infect and cross an in vitro human intestinal barrier model, indicating this epithelium as a potential viral entry site for neonates. Finally, this study confirms the existence of YFV transmission through breastfeeding in an animal model, highlighting the need to consider it among transmission risks.

microbiology↗

bioRxiv2024

A recombinant CHIKV-NLuc virus identifies chondrocytes as target of Chikungunya virus in a immunocompetent mouse model

First isolated in 1953 in Tanzania, the arthritogenic Chikungunya virus (CHIKV) re-emerged globally in 2005, leading to widespread outbreaks. Unlike other arboviruses, CHIKV predominantly induces symptomatic infections (72-96%), marked by fever, myalgia, polyarthralgia, and rash. Although rarely fatal, atypical forms such as encephalopathies can occur. Notably, 75.4% of patients experience persistent arthralgias for up to three years after the acute phase. Understanding CHIKVs pathophysiology in the joints is challenging due to the difficulties to obtain biological samples. The study employs a mouse model infected with a reporter virus expressing a Nano Luciferase to investigate the diseases transition to chronic arthritis. The murine model reveals viral replication in metatarsi joints, particularly in chondrocytes, confirmed in primary human chondrocytes undergoing viral-induced apoptosis. Ex vivo analysis confirmed viral replication in leg bones and articular cartilages, with histological evidence of focal erosive lesions and periarticular inflammation. The study further utilizes an in vivo imaging mouse model to monitor viral replication over time. Human chondrocytes prove susceptible to CHIKV infection, exhibiting active viral replication, bioluminescence activity, and increased viral production. CHIKV induced apoptosis, the upregulation of markers associated with cartilage remodeling and altered the cytokine production. This comprehensive study, utilizing advanced techniques and models, provides insights into CHIKVs ability to infect articular cartilages, shedding light on the mechanisms of chronic arthritis following infection.

microbiology↗

bioRxiv2024

Structures of the Foamy virus fusion protein reveal an unexpected link with the F protein of paramyxo- and pneumoviruses

Foamy viruses (FVs) constitute a subfamily of retroviruses. Their envelope glycoprotein (Env) drives the merger of viral and cellular membranes during entry into cells. The only available structures of retroviral Envs are those from human and simian immunodeficiency viruses from the subfamily of orthoretroviruses, which are only distantly related to the FVs. We report here the cryo-EM structures of the FV Env ectodomain in the pre- and post-fusion states, which demonstrate structural similarity with the fusion protein (F) of paramyxo- and pneumoviruses, implying an evolutionary link between the two viral fusogens. Based on the structural information on the FV Env in two states, we propose a mechanistic model for its conformational change, highlighting how the interplay of its structural elements could drive the structural rearrangement. The structural knowledge on the FV Env now provides a framework for functional investigations such as the FV cell tropism and molecular features controlling the Env fusogenicity, which can benefit the design of FV Env variants with improved features for use as gene therapy vectors.

microbiology↗

bioRxiv2022

Identifying the most probable mammal reservoir hosts for Monkeypox virus based on ecological niche comparisons

BackgroundPrevious human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contacts with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered. Methodology/Principal FindingsIn this study, we provide the full list of African mammal genera (and species) in which MPXV was previously detected and predict the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, we reconstruct the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases, and conduct overlap analyses with the ecological niches inferred for 99 mammal species in order to identify the most probable animal reservoir. Conclusions/SignificanceOur results show that the MPXV niche covers three African rainforests, the Congo Basin and Upper and Lower Guinean forests. The four mammal species showing the best niche overlap with MPXV are all arboreal rodents, including three squirrels, Funisciurus anerythrus, Funisciurus pyrropus, and Heliosciurus rufobrachium, and Graphiurus lorraineus. We conclude that the most probable MPXV reservoir is F. anerythrus based on two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection. SummaryMonkeypox (MPX) is an emerging zoonotic disease, endemic to rainforests of West and Central Africa, which manifests as a fever, swollen lymph nodes, and fatigue, followed by a rash with macular lesions progressing from papules to vesicles, pustules and scabs, usually on the face, hands, and feet for two to four weeks. The case fatality rate ranges from 1-3% in West Africa to 5-10% in Central Africa. The disease has been reported in 10 African countries between 1970 and today, with an increasing number of cases over the last decades and several exportations outside the continent, the last one in 2022 resulting in an epidemic involving mostly men who have sex with men, with more than 80,000 cases detected worldwide. Although MPX virus has been identified in many mammal species, most are likely secondary hosts and the reservoir host has yet to be discovered. In this study, we compare the predicted geographic distribution (ecological niche) of the MPX virus with that of 99 mammal species, and conclude that the most probable MPX reservoir is Thomass rope squirrel (Funisciurus anerythrus), followed by three other arboreal rodents, including two squirrels (Funisciurus pyrropus and Heliosciurus rufobrachium) and the Lorrain dormouse (Graphiurus lorraineus).

ecology↗

bioRxiv2022

Neutralization of zoonotic simian foamy viruses: genotype-specific epitopes within the receptor-binding domain

Infection with viruses of animal origin pose a significant threat to human populations. Simian foamy viruses (SFVs) are frequently transmitted to humans, in which they establish a life-long infection, with the persistence of replication-competent virus. However, zoonotic SFVs do not induce severe disease nor are they transmitted between humans. Thus, SFVs represent a model of zoonotic retroviruses that lead to a chronic infection successfully controlled by the human immune system. We previously showed that infected humans develop potent neutralizing antibodies (nAbs). Within the viral envelope (Env), the surface protein (SU) carries a variable region that defines two genotypes, overlaps with the receptor binding domain (RBD), and is the exclusive target of nAbs. However, its antigenic determinants are not understood. Here, we characterized nAbs present in plasma samples from SFV-infected individuals living in Central Africa. Neutralization assays were carried out in the presence of recombinant SU that compete with SU at the surface of viral vector particles. We defined the regions targeted by the nAbs using mutant SU proteins modified at the glycosylation sites, RBD functional subregions, and genotype-specific sequences that present properties of B-cell epitopes. We observed that nAbs target conformational epitopes. We identified three major epitopic regions: the loops at the apex of the RBD, which likely mediate interactions between Env protomers to form Env trimers, a loop located in the vicinity of the heparan binding site, and a region proximal to the highly conserved glycosylation site N8. We provide information on how nAbs specific for each of the two viral genotypes target different epitopes. Two common immune escape mechanisms, sequence variation and glycan shielding, were not observed. We propose a model according to which the neutralization mechanisms rely on the nAbs to block the Env conformational change and/or interfere with binding to susceptible cells. As the SFV RBD is structurally different from known retroviral RBDs, our data provide fundamental knowledge on the structural basis for the inhibition of viruses by nAbs.

microbiology↗

bioRxiv2022

The crystal structure of a simian Foamy Virus receptor binding domain provides clues about entry into host cells

The surface envelope glycoprotein (Env) of all retroviruses mediates virus binding to cells and fusion of the viral and cellular membranes. A structure-function relationship for the HIV Env that belongs to the Orthoretrovirus subfamily has been well established. Structural information is however largely missing for the Env of Foamy viruses (FVs), the second retroviral subfamily. FV Envs lack sequence similarity with their HIV counterpart. We present the X-ray structure of the receptor binding domain (RBD) of a simian FV Env at 2.6 [A] resolution, revealing two subdomains and an unprecedented fold. We have generated a model for the organization of the RBDs within the trimeric Env which indicates that the upper subdomain is important for stabilization of the full-length Env, and have demonstrated that residues K342, R343, R359 and R369 in the lower subdomain play key roles in the interaction of the RBD and viral particles with heparan sulfate.

microbiology↗

bioRxiv2022

The genomic landscape of contemporary western Remote Oceanians

The Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands, ~3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet, there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the worlds highest linguistic and cultural diversity. Here, we report new genome-wide data for 1,433 contemporary ni-Vanuatu from 29 different islands, including 287 couples. We find that ni-Vanuatu derive their East Asian- and Papuan-related ancestry from the same source populations and descend from relatively synchronous, sex-biased admixture events that occurred ~1,700-2,300 years ago, indicating a peopling history common to all the archipelago. However, East Asian-related ancestry proportions differ markedly across islands, suggesting that the Papuan-related population turnover was geographically uneven. Furthermore, we detect Polynesian ancestry arriving ~600-1,000 years ago to South Vanuatu in both Polynesian- and non-Polynesian-speaking populations. Lastly, we provide evidence for a tendency of spouses to carry similar genetic ancestry, when accounting for relatedness avoidance. The signal is not driven by strong genetic effects of specific loci or trait-associated variants, suggesting that it results instead from social assortative mating. Altogether, our findings provide insight into both the genetic history of ni-Vanuatu populations and how sociocultural processes have shaped the diversity of their genomes.

genomics↗

bioRxiv2019

Intragenic recruitment of NF-κB drives alternative splicing modifications upon activation by the viral oncogene TAX of HTLV-1.

The chronic NF-{kappa}B activation in inflammation and cancer has long been linked to persistent activation of NF-{kappa}B responsive gene promoters. However, NF-{kappa}B factors such as RELA also massively bind to gene bodies. Here, we demonstrate that the recruitment of RELA to intragenic regions regulates alternative splicing upon activation of NF-{kappa}B by the viral oncogene TAX of HTLV-1. Integrative analysis of RNA splicing and chromatin occupancy, combined with chromatin tethering assays, demonstrate that DNA-bound RELA interacts with and recruits the splicing regulator DDX17 in a NF-kB activation-dependent manner, leading to alternative splicing of target exons thanks to DDX17 RNA helicase activity. This NF-kB/DDX17 axis accounts for a major part of the TAX-induced alternative splicing landscape that mainly affects genes involved in oncogenic pathways. Collectively, our results demonstrate a physical and direct involvement of NF-{kappa}B in alternative splicing regulation, which significantly revisits our knowledge of HTLV-1 pathogenesis and other NF-{kappa}B-related diseases.

molecular biology↗