Biology subjects

Collin, V.

Publications and source records attributed to Collin, V..

7 recordsLinked to original sources

bioRxiv2026

Adequate coating and change in morphology increase the performances of silver nanoparticular biocides

Silver has been used as a biocide for centuries, mostly in health-oriented applications. However, as a biocide, silver is toxic not only to its intended targets, mainly bacteria and fungi, but also to all living cells. Because of this toxicity, it is desirable to use forms of silver that maximize the required biocidal activity while minimizing the amount of silver that will be released in the environment at the end of life of the product. Silver nano objects are a good compromise for such requirements. The high surface to volume ratio allows for good reactivity and thus good biocidal activity, while the small amount of silver present in nano objects allows for a limited environmental release at the product end of life. In this work, we tested three types of silver nano objects. The first type, polyvinylpyrrolidone-coated silver nanoparticles (nAg-PVP) were used as a control nanoparticle, as this type of nanoparticle is now widespread. We also manufactured and tested maltodextrin-coated silver nanoparticles (nAg-MD) and micrometric (20 {micro}m in two dimensions and a few nanometers in the third one) silver flakes ({micro}AgSF). For these three silver nano objects, we investigated the biocidal activity by stringent tests using both Staphylococcus aureus and Escherichia coli as target bacteria. In addition, we investigated toxicity on mammalian macrophages or keratinocytes cell lines, as well as on an insect hemocyte cell line. Our results showed that the two innovative silver nano objects (nAg-MD and even more {micro}AgSF), showed both a better bactericidal activity and a lesser toxicity than the reference nAg-PVP nanoparticles. In addition, we also checked that beyond toxicity, the silver nano objects did not induce an inflammatory reaction, making them safer to use.

pharmacology and toxicology↗

bioRxiv2026

Effects of polystyrene and polylactide nanoparticles on macrophages under a repeated exposure mode

Micro and nanoplastics are pollutants which concentration in different biotopes increases continuously over time, which poses the question of their potential effects on health. In animals, these micro and nanoplastics are recognized as particulate materials and thus handled by macrophages, which are therefore a key cell type to study. Most studies have used an experimental scheme in which the cells are exposed to a single dose of plastics, with a readout made immediately after exposure. However, this classical experimental scheme does not take into account the impact of biopersistence, nor the potential cellular adaptation that may take place when cells are exposed repeatedly to a low dose of plastics. We thus used a repeated exposure scheme, in order to better take into account these phenomena. Within this frame, we compared the macrophages responses to a persistent nanoplastic, i.e. polystyrene nanoparticles and to a biodegradable nanoplastic, i.e. polylactide, by a combination of proteomic and targeted experiments. Our results show that under this repeated exposure scheme, the proteome changes were of a lesser (for PS) or similar (for PLA) extent than under the acute exposure mode, indicating cell adaptation. However, PLA particles induced mitochondrial dysfunction and depression of response to bacterial molecules perceived as danger signals, such as lipopolysaccharide. Polystyrene nanoparticles also induced a slight alteration of the immune functions of macrophages. This indicates harmful effects even in the repeated exposure scheme.

pharmacology and toxicology↗

bioRxiv2025

Effects of true to life polyethylene terephthalate and polycaprolactone nanoparticles on macrophages under a repeated exposure mode.

Micro and nanoplastics are pollutants which concentration in different biotopes increases continuously over time, which poses the question of their potential effects on health. In animals, these micro and nanoplastics are recognized as particulate materials and thus handled by macrophages, either directly in the case of lung exposure, or after the particles have crossed the epithelial barriers in case of oral or dermal exposure. It is thus important to study the potential effects of micro and nanoplastics on macrophages. Most studies have used an experimental scheme in which the cells of interest are exposed to a single dose of plastics, and where the readout of the studied parameters is made immediately after exposure. However, this classical experimental scheme does not take into account the impact of biopersistence, nor the potential cellular adaptation that may take place when cells are exposed repeatedly to a low dose of plastics. We thus used a repeated exposure scheme, in order to better take into account these phenomena. Within this frame, we compared the macrophages responses to a persistent nanoplastic, i.e. true-to-life polyethylene terephthalate nanoparticles and to a biodegradable nanoplastic, i.e. polycaprolactone, by a combination of proteomic and targeted experiments. Our results show that under this repeated exposure scheme, the proteome changes were of a lesser extent than under the acute exposure mode, indicating cell adaptation. However, polyethylene terephthalate nanoparticles induced oxidative stress and a pro-inflammatory response, while polycaprolactone nanoparticles induced a depression of macrophages functions, indicating harmful effects even in the repeated exposure scheme.

pharmacology and toxicology↗

bioRxiv2024

Biobased, Biodegradable but not bio-neutral: about the effects of polylactic acid nanoparticles on macrophages

Plastics are persistent pollutants, because of their slow degradation, which suggests that they may lead to cumulative and/or delayed adverse effects due to their progressive accumulation over time. Macroplastics produced by human activity are released in the environment, where they degrade into micro and nanoplastics that are very easily uptaken by a wide variety of organisms, including humans. Microplastics and nanoplastics being particulates, they are handled in the body by specialized cells such as macrophages (or their evolutionary counterparts), where they can elicit a variety of responses. One solution to alleviate the problems due to biopersistence, such as accumulation over life, would be to use biodegradable plastics. One of the emerging biodegradable plastics being polylactide, we decided to test the responses of macrophages to polylactide nanoparticles, using a combination of untargeted proteomics and targeted validation experiments. Proteomics showed important adaptive changes in the proteome in response to exposure to polylactide nanoparticles. These changes affected for example mitochondrial, cytoskeletal and lysosomal proteins, but also proteins implicated in immune functions or redox homeostasis. Validation experiments showed that many of these changes were homeostatic, with no induced oxidative stress and no gross perturbation of the mitochondrial function. However, polylactide particles altered the immune functions such as phagocytosis (-20%) or cytokine production (2-fold increase for TNF production), which may translate into a decreased ability to macrophages to respond to bacterial infections. Furthermore, polylactide particles also induced moderate cross-toxicity with some quinones such as phenanthrene quinone, a combustion by-product that is a suspected carcinogen.

pharmacology and toxicology↗

bioRxiv2021

The immediate early protein 1 of the human herpesvirus 6B counteracts NBS1 and prevents homologous recombination repair pathways

Viral infection often trigger an ATM-dependent DNA damage response (DDR) in host cells that suppresses viral replication. To counteract this antiviral surveillance system, viruses evolved different strategies to induce the degradation of the MRE11/RAD50/NBS1 (MRN) complex and prevent subsequent DDR signaling. Here, we report that human herpesvirus 6B (HHV-6B) infection causes genomic instability by suppressing the host cells ability to induce ATM-dependent signaling pathways. Expression of immediate early protein 1 (IE1) phenocopies this phenotype and blocks further homology-directed double-strand break (DSB) repair. In contrast to other viruses, IE1 does not affect the stability of the MRN complex. Instead, it uses two distinct domains to inhibit ATM serine/threonine kinase (ATM) activation at DSBs. Structure-based analyses revealed that the N-terminal domain of IE1 interacts with the BRCA1 C-terminal domain 2 of nibrin (NBN, also known as NBS1), while ATM inhibition is attributable to on its C-terminal domain. Consistent with the role of the MRN complex in antiviral responses, NBS1 depletion resulted in increased HHV-6B replication in infected cells. However, in semi-permissive cells, viral integration of HHV-6B into the telomeres was not strictly dependent on NBS1, supporting models where this process occurs via telomere elongation rather than through DNA repair. Interestingly, as IE1 expression has been detected in cells of subjects with inherited chromosomally-integrated form of HHV-6B (iciHHV-6B), a condition associated with several health conditions, our results raise the possibility of a link between genomic instability and the development of iciHHV-6-associated diseases. Significance StatementMany viruses have evolved ways to inhibit DNA damage signaling, presumably to prevent infected cells from activating an antiviral response. Here, we show that this is also true for human herpesvirus 6B (HHV-6B), through its immediate early protein 1 (IE1). However, in contrast to adenovirus immediate early proteins, HHV-6B IE1 is recruited to double-strand breaks in an NBS1-dependent manner and inhibits ATM serine/threonine kinase activation. Characterizing this phenotype revealed a unique mechanism by which HHV-6B manipulates DNA damage signaling in infected cells. Consistently, viral replication is restricted by the MRN complex in HHV-6B infected cells. Viral integration of HHV-6B into the hosts telomeres is not strictly dependent on NBS1, challenging current models where integration occurs through homology-directed repair.

microbiology↗

bioRxiv2019

Modulation and recruitment of TRF2 at viral telomeres during human herpesvirus 6A/B infection

Human herpesviruses 6A and 6B (HHV-6A/B) can integrate their genomes into the telomeres of host chromosomes. The HHV-6A/B genomes contain telomeric repeats essential for integration. Whether HHV-6A/B infections impact telomere homeostasis remains to be studied. We report that during infection, a massive increase in telomeric signals is observed. Such telomeric signals are detected in viral replication compartments (VRC) that colocalize with the viral IE2 and P41 proteins. Infection with HHV-6A mutants lacking telomeric repeats did not reproduce this phenotype. HHV-6A/B infections lead to increased expression of three shelterin genes, TRF1, TRF2 and TPP1. TRF2 was recruited to VRC and binding to the HHV-6A/B telomeric repeats demonstrated by chromatin immunoprecipitation and ELISA. Lastly, the HHV-6A IE2 protein colocalized with shelterin proteins at telomeres during infection. In summary, HHV-6A/B infections results in an excess of telomeric repeats that stimulates the expression of shelterin genes. TRF2 binds to viral telomeres during infection and localizes with HHV-6A IE2 protein. Our results highlight a potential role for shelterin complex proteins and IE2 during infection and possibly during integration of HHV-6A/B into host chromosomes.

microbiology↗

bioRxiv2018

Role of PML-Nuclear Bodies in Human Herpesvirus 6A and 6B Genome Integration.

Human herpesviruses 6A and 6B (HHV-6A/B) are two betaherpesviruses that readily integrate their genomes into the telomeres of human chromosomes. To date, the cellular or viral proteins that facilitate HHV-6A/B integration remain elusive. In the present study, we demonstrate that the immediate early protein 1 (IE1) of HHV-6A/B colocalizes with telomeres during infection. Moreover, IE1 associates with PML-NBs, a nuclear complex that regulates multiples cellular mechanism including DNA repair and antiviral responses. Furthermore, we could demonstrate that IE1 targets all PML isoforms and that both proteins colocalize at telomeres. To determine the role of PML in HHV-6A/B integration, we generated PML knockout cell lines using CRISPR/Cas9. Intriguingly, in the absence of PML, the IE1 protein could still localize to telomeres albeit less frequently. More importantly, HHV-6A/B integration was impaired in the absence of PML, indicating that it plays a role in the integration process. Taken together, we identified the first cellular protein that aids in the integration of HHV-6A/B and shed light on this targeted integration mechanism.\n\nAuthor summaryHuman herpesviruses type 6A and 6B are relatively common viruses whose infections can be life threatening in patients with a compromised immune system. A rather unique feature of these viruses is their ability to integrate their genome in human chromosomes. Integration takes place is a specialized region of the chromosomes known as telomeres, a region that controls cellular lifespan. To date, the mechanisms leading to HHV-6A and HHV-6B integration remain elusive. Our laboratory has identified that the IE1 protein of HHV-6A and HHV-6B target the telomeres. Moreover, we have shown that IE1 associates with a cellular protein, PML, that is responsible for the regulation of important cellular mechanisms such as the life span of cells and DNA repair. Hence, we studied the role of PML in HHV-6 integration. Our study demonstrates that in absence of PML, the HHV-6A and HHV-6B integrate 50-70% less frequently. Thus, our study unveils the first cellular protein involved in HHV-6A and HHV-6 chromosomal integration.

microbiology↗