Sumoylation coordinates the repression of inflammatory and anti-viral gene-expression programs during innate sensing.

Innate sensing of pathogens initiates inflammatory cytokine responses that need to be tightly controlled. We found here that after engagement of Toll-like receptors (TLRs) in myeloid cells, deficient sumoylation caused increased secretion of transcription factor NF-κB-dependent inflammatory cytokines and a massive type I interferon signature. In mice, diminished sumoylation conferred susceptibility to endotoxin shock and resistance to viral infection. Overproduction of several NF-κB-dependent inflammatory cytokines required expression of the type I interferon receptor, which identified type I interferon as a central sumoylation-controlled hub for inflammation. Mechanistically, the small ubiquitin-like modifier SUMO operated from a distal enhancer of the gene encoding interferon-ß (Ifnb1) to silence both basal and stimulus-induced activity of the Ifnb1 promoter. Therefore, sumoylation restrained inflammation by silencing Ifnb1 expression and by strictly suppressing an unanticipated priming by type I interferons of the TLR-induced production of inflammatory cytokines.

Successive passaging of a plant-associated microbiome reveals robust habitat and host genotype-dependent selection.

There is increasing interest in the plant microbiome as it relates to both plant health and agricultural sustainability. One key unanswered question is whether we can select for a plant microbiome that is robust after colonization of target hosts. We used a successive passaging experiment to address this question by selecting upon the tomato phyllosphere microbiome. Beginning with a diverse microbial community generated from field-grown tomato plants, we inoculated replicate plants across 5 plant genotypes for 4 45-d passages, sequencing the microbial community at each passage. We observed consistent shifts in both the bacterial (16S amplicon sequencing) and fungal (internal transcribed spacer region amplicon sequencing) communities across replicate lines over time, as well as a general loss of diversity over the course of the experiment, suggesting that much of the naturally observed microbial community in the phyllosphere is likely transient or poorly adapted within the experimental setting. We found that both host genotype and environment shape microbial composition, but the relative importance of genotype declines through time. Furthermore, using a community coalescence experiment, we found that the bacterial community from the end of the experiment was robust to invasion by the starting bacterial community. These results highlight that selecting for a stable microbiome that is well adapted to a particular host environment is indeed possible, emphasizing the great potential of this approach in agriculture and beyond. In light of the consistent response of the microbiome to selection in the absence of reciprocal host evolution (coevolution) described here, future studies should address how such adaptation influences host health.

The extrachromosomal circular DNAs of the rice blast pathogen Magnaporthe oryzae contain a wide variety of LTR retrotransposons, genes, and effectors.

BACKGROUND: One of the ways genomes respond to stress is by producing extrachromosomal circular DNAs (eccDNAs). EccDNAs can contain genes and dramatically increase their copy number. They can also reinsert into the genome, generating structural variation. They have been shown to provide a source of phenotypic and genotypic plasticity in several species. However, whole circularome studies have so far been limited to a few model organisms. Fungal plant pathogens are a serious threat to global food security in part because of their rapid adaptation to disease prevention strategies. Understanding the mechanisms fungal pathogens use to escape disease control is paramount to curbing their threat. RESULTS: We present a whole circularome sequencing study of the rice blast pathogen, Magnaporthe oryzae. We find that M. oryzae has a highly diverse circularome that contains many genes and shows evidence of large LTR retrotransposon activity. We find that genes enriched on eccDNAs in M. oryzae occur in genomic regions prone to presence-absence variation and that disease-associated genes are frequently on eccDNAs. Finally, we find that a subset of genes is never present on eccDNAs in our data, which indicates that the presence of these genes on eccDNAs is selected against. CONCLUSIONS: Our study paves the way to understanding how eccDNAs contribute to adaptation in M. oryzae. Our analysis also reveals how M. oryzae eccDNAs differ from those of other species and highlights the need for further comparative characterization of eccDNAs across species to gain a better understanding of these molecules.

Community mental health literacy in Tshwane region 1: A quantitative study.

Background: Although mental health literacy is a major determining factor of mental health outcomes and functional capacity of individuals, there is dearth of research on the issue in South Africa. Aim: To assess the literacy of three mental disorders, namely major depressive disorder (MDD), schizophrenia and generalised anxiety disorder (GAD) and to compare the resultant assumed literacy level between urban and townships participants. Setting: Five clinics of region 1 in Tshwane, South Africa. Method: A cross-sectional descriptive study was performed between November 2019 and January 2020. A total of 385 questionnaires were distributed equally in all five clinics. By means of questions about three fictive cases with clinical pictures indicative of MDD, schizophrenia and GAD the following were assessed: recognising a mental disorder, identifying the cause and knowledge about what would help best. Results: The majority of participants (67.3%) recognised the clinical picture indicative of schizophrenia as a mental disorder, almost half of the participants (49.9%) recognised the clinical picture indicative of MDD as a mental disorder, whilst just more than one third (36.3%) of participants recognised the clinical picture GAD as a mental disorder. Concerning the causes for the clinical pictures, most participants indicated that stress was the cause for MDD and GAD (77.4% and 68.1%, respectively), whilst indicating that biological or psychological (59.5%) causes are relevant to the clinical picture indicative of schizophrenia symptoms. Fewer participants indicated supernatural causes for any of the clinical case (MDD: 2.6%; schizophrenia 15.3%; GAD 4.2%). Most participants chose professional help as the best option for all three cases (MDD 81.3%, schizophrenia 82.2%, GAD 66.1%). The indicators for health literacy in this study show that urban participants had better knowledge than township participants across all questions about the cases. Conclusion: Overall, the study indicated a variable knowledge regarding the three mental disorders in region 1 of Tshwane and variable literacy levels in townships compared with urban settings. The results indicate that awareness campaigns should focus on the deficient areas.

Influence of first- and second-generation antipsychotics on anthropometric parameters of male psychiatric patients.

Background: The use of antipsychotic medication, particularly second generation antipsychotics (SGAs) is a major risk factor for cardiovascular disease in people with severe mental illness (SMI). Few studies have compared body measures of people with SMI taking first generation antipsychotics (FGAs) to those taking SGAs. Aim: We compare body measures between long-term male inpatients using either FGAs or SGAs. Setting: The study was conducted at Weskoppies Psychiatric Hospital, in Pretoria, Gauteng. Methods: A total of 30 patients were selected from a list of male inpatients and were included in our study. Each participant had the following anthropometric measures done and these were compared between the two groups: Waist circumference (WC), body mass index (BMI), waist to hip ratio (WHR), waist to height ratio (WHtR) and hip circumference (HC). Hospital records were used to record demographic variables, diagnosis, comorbid disease and psychotropic medication for each participant. Results: Participants in the FGA and SGA groups had similar body measures, resulting in similar BMI, WHR and WHtR. Participants had a mean HC of 100.5 cm, 95% confidence interval (CI) (97.68, 103.22). BMI ranged from 21.87 kg/m² to 37.65 kg/m², with an overall mean of 28.5 kg/m², 95% CI (26.69, 30.22). Participants had a mean WHtR of 0.59, 95% CI (0.56, 0.61). Participants had a mean WC of 100.6 cm and 95% CI (96.26, 104.87), and the mean WHR of both groups was 1.0. Conclusion: Participants using FGAs and SGAs had similar body measures, and these indicated that this sample of male inpatients with SMI is at high risk for CVD.

Non-Contact Radiofrequency Inductive Sensor for the Dielectric Characterization of Burn Depth in Organic Tissues.

A flat circular transmission line-based 300 MHz resonator was implemented for the non-contact assessment of burn depths in biological tissues. Used as a transmit-and-receive sensor, it was placed at a 2 mm distance from organic material test samples (pork fillet samples) which were previously burned on their surface in various heating conditions involving different temperatures, durations, and procedures. Data extracted from the sensor by means of a distant monitoring coil were found to clearly correlate with the depth of burn observed in the tissue samples (up to 40% sensor output changes for a 7 mm burn depth) and with the heating conditions (around 5% sensor output changes observed in samples burned with identical heating procedures but at two different temperatures-75 °C and 150 °C-and around 40% sensor output changes observed between samples heated at the same temperature but with different heating procedures). These results open the way for the development of easy-to-implement assessment and monitoring techniques for burns, e.g., integrated in wearable medical dressing-like monitoring devices.

Influence of the Porosity of Polymer Foams on the Performances of Capacitive Flexible Pressure Sensors.

This paper reports on the study of microporous polydimethylsiloxane (PDMS) foams as a highly deformable dielectric material used in the composition of flexible capacitive pressure sensors dedicated to wearable use. A fabrication process allowing the porosity of the foams to be adjusted was proposed and the fabricated foams were characterized. Then, elementary capacitive pressure sensors (15 × 15 mm2 square shaped electrodes) were elaborated with fabricated foams (5 mm or 10 mm thick) and were electromechanically characterized. Since the sensor responses under load are strongly non-linear, a behavioral non-linear model (first order exponential) was proposed, adjusted to the experimental data, and used to objectively estimate the sensor performances in terms of sensitivity and measurement range. The main conclusions of this study are that the porosity of the PDMS foams can be adjusted through the sugar:PDMS volume ratio and the size of sugar crystals used to fabricate the foams. Additionally, the porosity of the foams significantly modified the sensor performances. Indeed, compared to bulk PDMS sensors of the same size, the sensitivity of porous PDMS sensors could be multiplied by a factor up to 100 (the sensitivity is 0.14 %.kPa-1 for a bulk PDMS sensor and up to 13.7 %.kPa-1 for a porous PDMS sensor of the same dimensions), while the measurement range was reduced from a factor of 2 to 3 (from 594 kPa for a bulk PDMS sensor down to between 255 and 177 kPa for a PDMS foam sensor of the same dimensions, according to the porosity). This study opens the way to the design and fabrication of wearable flexible pressure sensors with adjustable performances through the control of the porosity of the fabricated PDMS foams.

Patients' opinions about referral from a tertiary specialist psychiatric hospital to primary healthcare.

BACKGROUND: Referral of patients from tertiary specialist psychiatric hospitals to primary healthcare settings is a worldwide goal. This is of particular importance in South Africa with its considerable burden of mental disorders and limited resources. However, patients are often reluctant to be referred and studies have shown that patients may prefer a dedicated psychiatric service over an integrated primary healthcare service. AIM: This study explored the opinions of patients receiving care at a tertiary psychiatric hospital's outpatient department (OPD) about referral to a primary healthcare clinic (PHCC). SETTING: The study was conducted at Weskoppies Psychiatric Hospital OPD. METHODS: This was a qualitative study based on grounded theory. Participants were recruited through purposive-theoretical sampling. Data were collected by means of individual interviews and mini-essays. RESULTS: From the 80 participants, 18 had individual interviews and 62 wrote mini-essays. Thirty-nine participants had previously attended a PHCC, while 41 had not. Perceived advantages of referral to PHCCs included: close proximity to participants' homes, resulting in saving on travelling time and transport costs, as well as the convenience of receiving psychiatric and other medical treatment at the same healthcare facility. Perceived disadvantages of PHCCs included: unavailability of treatment; lack of doctor-based care; lack of specialised care; loss of established relationships with hospital healthcare workers; mistreatment by PHCC nursing staff; longer waiting times; more stigmatisation. CONCLUSION: The perceived disadvantages of referral from a tertiary psychiatric hospital to a PHCC outweighed the perceived advantages. Nonetheless, participants expressed willingness for such a referral if their concerns were addressed.

Inhibition of mTORC1 Enhances the Translation of Chikungunya Proteins via the Activation of the MnK/eIF4E Pathway.

Chikungunya virus (CHIKV), the causative agent of a major epidemic spanning five continents, is a positive stranded mRNA virus that replicates using the cell's cap-dependent translation machinery. Despite viral infection inhibiting mTOR, a metabolic sensor controls cap-dependent translation, viral proteins are efficiently translated. Rapalog treatment, silencing of mtor or raptor genes, but not rictor, further enhanced CHIKV infection in culture cells. Using biochemical assays and real time imaging, we demonstrate that this effect is independent of autophagy or type I interferon production. Providing in vivo evidence for the relevance of our findings, mice treated with mTORC1 inhibitors exhibited increased lethality and showed a higher sensitivity to CHIKV. A systematic evaluation of the viral life cycle indicated that inhibition of mTORC1 has a specific positive effect on viral proteins, enhancing viral replication by increasing the translation of both structural and nonstructural proteins. Molecular analysis defined a role for phosphatidylinositol-3 kinase (PI3K) and MAP kinase-activated protein kinase (MnKs) activation, leading to the hyper-phosphorylation of eIF4E. Finally, we demonstrated that in the context of CHIKV inhibition of mTORC1, viral replication is prioritized over host translation via a similar mechanism. Our study reveals an unexpected bypass pathway by which CHIKV protein translation overcomes viral induced mTORC1 inhibition.

Distinct genomic contexts predict gene presence-absence variation in different pathotypes of Magnaporthe oryzae.

Fungi use the accessory gene content of their pangenomes to adapt to their environments. While gene presence-absence variation contributes to shaping accessory gene reservoirs, the genomic contexts that shape these events remain unclear. Since pangenome studies are typically species-wide and do not analyze different populations separately, it is yet to be uncovered whether presence-absence variation patterns and mechanisms are consistent across populations. Fungal plant pathogens are useful models for studying presence-absence variation because they rely on it to adapt to their hosts, and members of a species often infect distinct hosts. We analyzed gene presence-absence variation in the blast fungus, Magnaporthe oryzae (syn. Pyricularia oryzae), and found that presence-absence variation genes involved in host-pathogen and microbe-microbe interactions may drive the adaptation of the fungus to its environment. We then analyzed genomic and epigenomic features of presence-absence variation and observed that proximity to transposable elements, gene GC content, gene length, expression level in the host, and histone H3K27me3 marks were different between presence-absence variation genes and conserved genes. We used these features to construct a model that was able to predict whether a gene is likely to experience presence-absence variation with high precision (86.06%) and recall (92.88%) in M. oryzae. Finally, we found that presence-absence variation genes in the rice and wheat pathotypes of M. oryzae differed in their number and their genomic context. Our results suggest that genomic and epigenomic features of gene presence-absence variation can be used to better understand and predict fungal pangenome evolution. We also show that substantial intra-species variation can exist in these features.

Lemierre's syndrome: A rare complication of acute bacterial pharyngitis.

Lemierre's syndrome is a rare clinical syndrome of septic thrombophlebitis following a bacterial oropharyngeal infection. Lemierre's syndrome can be difficult to recognise and has significant morbidity. We report the case of a young man with Lemierre's syndrome caused by Streptococcus pyogenes, who responded well to 2 weeks of beta-lactam therapy. Contributions: This case report summarises the key presenting features of Lemierre's syndrome and provides a brief literature review considering the South African context.

Unraveling the complex interplay between anti-tumor immune response and autoimmunity mediated by B cells and autoantibodies in the era of anti-checkpoint monoclonal antibody therapies.

The intricate relationship between anti-tumor immunity and autoimmunity is a complex yet crucial aspect of cancer biology. Tumor microenvironment often exhibits autoimmune features, a phenomenon that involves natural autoimmunity and the induction of humoral responses against self-antigens during tumorigenesis. This induction is facilitated by the orchestration of anti-tumor immunity, particularly within organized structures like tertiary lymphoid structures (TLS). Paradoxically, a significant number of cancer patients do not manifest autoimmune features during the course of their illness, with rare instances of paraneoplastic syndromes. This discrepancy can be attributed to various immune-mediated locks, including regulatory or suppressive immune cells, anergic autoreactive lymphocytes, or induction of effector cells exhaustion due to chronic stimulation. Overcoming these locks holds the risk to induce autoimmune mechanisms during cancer progression, a phenomenon notably observed with anti-immune checkpoint therapies, in contrast to more conventional treatments like chemotherapy or radiotherapy. Therefore, the challenge arises in managing immune-related adverse events (irAEs) induced by immune checkpoint inhibitors treatment, as decoupling them from the anti-tumor activity poses a significant clinical dilemma. This review summarizes recent advances in understanding the link between B-cell driven anti-tumor responses and autoimmune reactions in cancer patients, and discusses the clinical implications of this relationship.

IRGM is a common target of RNA viruses that subvert the autophagy network.

Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity.

Autophagy during viral infections: a double-edge sword.

During evolution, organisms were confronted with different environmental pressures leading to selective evolution of different intracellular pathways. Autophagy, an ancestral cellular mechanism involved in cell homeostasis and survival, provides an interesting example of this biologic concept. The constant dialog between viral infections and mechanisms of host protection has scripted the evolving relationship between autophagy and viruses, with some infectious agents being controlled by autophagy; whereas others, perhaps more opportunistic viruses, have adapted to manipulate autophagy for their own benefit.

Distinct genomic contexts predict gene presence-absence variation in different pathotypes of a fungal plant pathogen.

Background: Fungi use the accessory segments of their pan-genomes to adapt to their environments. While gene presence-absence variation (PAV) contributes to shaping these accessory gene reservoirs, whether these events happen in specific genomic contexts remains unclear. Additionally, since pan-genome studies often group together all members of the same species, it is uncertain whether genomic or epigenomic features shaping pan-genome evolution are consistent across populations within the same species. Fungal plant pathogens are useful models for answering these questions because members of the same species often infect distinct hosts, and they frequently rely on gene PAV to adapt to these hosts. Results: We analyzed gene PAV in the rice and wheat blast fungus, Magnaporthe oryzae, and found that PAV of disease-causing effectors, antibiotic production, and non-self-recognition genes may drive the adaptation of the fungus to its environment. We then analyzed genomic and epigenomic features and data from available datasets for patterns that might help explain these PAV events. We observed that proximity to transposable elements (TEs), gene GC content, gene length, expression level in the host, and histone H3K27me3 marks were different between PAV genes and conserved genes, among other features. We used these features to construct a random forest classifier that was able to predict whether a gene is likely to experience PAV with high precision (86.06%) and recall (92.88%) in rice-infecting M. oryzae. Finally, we found that PAV in wheat- and rice-infecting pathotypes of M. oryzae differed in their number and their genomic context. Conclusions: Our results suggest that genomic and epigenomic features of gene PAV can be used to better understand and even predict fungal pan-genome evolution. We also show that substantial intra-species variation can exist in these features.

Intraspecific Variation of Transposable Elements Reveals Differences in the Evolutionary History of Fungal Phytopathogen Pathotypes.

Transposable elements (TEs) contribute to intraspecific variation and play important roles in the evolution of fungal genomes. However, our understanding of the processes that shape TE landscapes is limited, as is our understanding of the relationship between TE content, population structure, and evolutionary history of fungal species. Fungal plant pathogens, which often have host-specific populations, are useful systems in which to study intraspecific TE content diversity. Here, we describe TE dynamics in five lineages of Magnaporthe oryzae, the fungus that causes blast disease of rice, wheat, and many other grasses. We identified differences in TE content across these lineages and showed that recent lineage-specific expansions of certain TEs have contributed to overall greater TE content in rice-infecting and Setaria-infecting lineages. We reconstructed the evolutionary histories of long terminal repeat-retrotransposon expansions and found that in some cases they were caused by complex proliferation dynamics of one element and in others by multiple elements from an older population of TEs multiplying in parallel. Additionally, we found evidence suggesting the recent transfer of a DNA transposon between rice- and wheat-infecting M. oryzae lineages and a region showing evidence of homologous recombination between those lineages, which could have facilitated such a transfer. By investigating intraspecific TE content variation, we uncovered key differences in the proliferation dynamics of TEs in various pathotypes of a fungal plant pathogen, giving us a better understanding of the evolutionary history of the pathogen itself.

Acute Influenza Infection Promotes Lung Tumor Growth by Reprogramming the Tumor Microenvironment.

One billion people worldwide get flu every year, including patients with non-small cell lung cancer (NSCLC). However, the impact of acute influenza A virus (IAV) infection on the composition of the tumor microenvironment (TME) and the clinical outcome of patients with NSCLC is largely unknown. We set out to understand how IAV load impacts cancer growth and modifies cellular and molecular players in the TME. Herein, we report that IAV can infect both tumor and immune cells, resulting in a long-term protumoral effect in tumor-bearing mice. Mechanistically, IAV impaired tumor-specific T-cell responses, led to the exhaustion of memory CD8+ T cells and induced PD-L1 expression on tumor cells. IAV infection modulated the transcriptomic profile of the TME, fine-tuning it toward immunosuppression, carcinogenesis, and lipid and drug metabolism. Consistent with these data, the transcriptional module induced by IAV infection in tumor cells in tumor-bearing mice was also found in human patients with lung adenocarcinoma and correlated with poor overall survival. In conclusion, we found that IAV infection worsened lung tumor progression by reprogramming the TME toward a more aggressive state.

Autophagy-Related Gene Signature Highlights Metabolic and Immunogenic Status of Malignant Cells in Non-Small Cell Lung Cancer Adenocarcinoma.

Autophagy is a self-degradative mechanism involved in many biological processes, including cell death, survival, proliferation or migration. In tumors, autophagy plays an important role in tumorigenesis as well as cancer progression and resistance to therapies. Usually, a high level of autophagy in malignant cells has been associated with tumor progression and poor prognostic for patients. However, the investigation of autophagy levels in patients remains difficult, especially because quantification of autophagy proteins is challenging in the tumor microenvironment. In this study, we analyzed the expression of autophagy genes in non-small cell lung (NSCLC) cancer patients using public datasets and revealed an autophagy gene signature for proliferative and immune-checkpoint-expressed malignant cells in lung adenocarcinoma (LUAD). Analysis of autophagy-related gene expression profiles in tumor and adjacent tissues revealed differential signatures, namely signature A (23 genes) and signature B (12 genes). Signature B correlated with a bad prognosis and poor overall and disease-specific survival. Univariate and multivariate analyses revealed that this signature was an independent factor for prognosis. Moreover, patients with high expression of signature B exhibited more genes related to proliferation and fewer genes related to immune cells or immune response. The analysis of datasets from sorted fresh tumor cells or single cells revealed that signature B is predominantly represented in malignant cells, with poor expression in pan-immune population or in fibroblast or endothelial cells. Interestingly, autophagy was increased in malignant cells exhibiting high levels of signature B, which correlated with an elevated expression of genes involved in cell proliferation and immune checkpoint signaling. Taken together, our analysis reveals a novel autophagy-based signature to define the metabolic and immunogenic status of malignant cells in LUAD.

[Autophagy modulation by viruses: An important role in tumor progression]. / L'autophagie modulée par les virus - Un rôle dans la progression tumorale.

Autophagy is an important process for cellular homeostasis at critical steps of development or in response to environmental stress. In the context of cancers, autophagy has a significant impact on tumor occurrence and tumor cell growth. On the one hand, autophagy limits the transformation of precancerous cells into cancer cells at an early stage. However, on the other hand, it promotes cell survival, cell proliferation, metastasis and resistance to anti-tumor therapies in more advanced tumors. Autophagy can be induced by a variety of extracellular and intracellular stimulus. Viral infections have often been associated with a modulation of autophagy, with variable impacts on viral replication and on the survival of infected cells depending on the model studied. In a tumor context, the modulation of autophagy induced by the viral infection of tumor cells seems to have a significant impact on tumor progression. The aim of this review article is to present recent findings regarding the consequences of autophagy disturbance by viral infections on tumor behavior.

TITLE: L'autophagie modulée par les virus - Un rôle dans la progression tumorale. ABSTRACT: L'autophagie est un processus métabolique important pour maintenir l'homéostasie cellulaire à des moments critiques du développement et/ou en réponse à un stress environnemental. Cela est particulièrement pertinent dans le cas des cancers, pour lesquels il a été montré que l'autophagie a un impact important sur leur survenue et sur la croissance tumorale. D'une part, elle limite la transformation cancéreuse des cellules précancéreuses à un stade précoce, mais, d'autre part, elle favorise la survie et la prolifération cellulaires, les métastases et la résistance aux thérapies anti-tumorales dans les tumeurs plus avancées. L'autophagie peut être induite par une grande variété de stimulus extracellulaires et intracellulaires. Les infections virales ont souvent été associées à une modulation de l'autophagie, dont l'impact sur la réplication virale ou la survie des cellules infectées diffère selon le modèle étudié. Dans un contexte tumoral, certains mécanismes moléculaires complexes par lesquels la modulation de l'autophagie par les virus peut influencer le développement des cellules précancéreuses ou cancéreuses ont été révélés. Cette revue présente les découvertes récentes concernant les répercussions d'une perturbation de l'autophagie par l'infection virale sur la survenue et la progression des tumeurs cancéreuses.

Multisystem cytomegalovirus end-organ disease in a patient with advanced HIV.

Cytomegalovirus (CMV) infection is common in people living with HIV, but multisystem CMV end-organ disease (EOD) is rare following the introduction of effective antiretroviral therapy. We present the case of a patient with advanced HIV and multisystem manifestations of CMV EOD. Contributions: This case report highlights the potential morbidity and mortality associated with CMV disease in patients with advanced HIV. Clinicians should be vigilant in considering CMV EOD in patients with advanced HIV and visual, neurological and gastointestinal symptoms.