Introduction:Immune checkpoint inhibitor (ICI)-induced acute interstitial nephritis (AIN) (ICI-AIN) is the leading cause of ICI-associated acute kidney injury (AKI). ICI-AIN is characterized by mononuclear immune infiltrates, although the mechanisms behind their toxicity remain unclear. We aimed to characterize these infiltrates in kidney biopsies and assess their correlation with clinical outcomes and therapeutic responses. Methods:We retrospectively analyzed 49 biopsy-proven ICI-AIN cases using multiplex immunofluorescence to quantify immune cells (macrophages, neutrophils, B cells, T cells, and plasmocytes). Unsupervised clustering was used to identify patient groups, which we then correlated with clinical presentation and outcomes. Finally, we explored the role of C5a/C5aR1 in neutrophil recruitment. Results:Unsupervised clustering revealed 3 immune phenotypes as follows: (i) low mononuclear (cluster 1), (ii) high mononuclear (cluster 2), and (iii) neutrophil-rich (cluster 3). Cluster 3 was associated with higher systemic inflammation (C-reactive protein: 84 vs. 15-24 mg/l, P = 0.0002; neutrophil-to-lymphocyte ratio (NLR): 7 vs. 3.2-2.3, P < 0.0001) and more severe initial AKI (peak creatinine: 360 vs. 215-208 μmol/l, P = 0.0001). Histologically, it was marked by granular casts and neutrophilic tubulitis (P < 0.0001). Despite the pyelonephritis-like appearance, urine cultures and metatranscriptomic analysis both ruled out infection. At 12 months, renal response rates to steroids were 93% (cluster 2), 67% (cluster 1), and 38% (cluster 3) (P = 0.004). Relapses occurred more frequently in cluster 3 (38% vs. 11% in cluster 1, 0% in cluster 2, P = 0.01). Urine C5a correlated with C5aR1+ neutrophil infiltration (rho = 0.78). Conclusion:Our findings identify distinct ICI-AIN subtypes, with a neutrophil-rich cluster linked to complement activation and poor prognosis, offering insights into refining diagnosis and treatment strategies.

Pigeon paramyxovirus type 1 (PPMV-1) is a genotype of avian paramyxovirus type 1 that uses species of the family Columbidae as reservoir species. We report fatal PPMV-1 encephalitis in a human without immunosuppression or travel history outside metropolitan France. Postmortem analyses revealed PPMV-1 in tissues, underscoring that physicians should consider this potential diagnosis.

Once passed into the bloodstream, bacterial pathogens have a limited time to interact with permissive receptors at the surface of host cells. Neisseria meningitidis has developed an extremely effective strategy allowing it to find its receptors in a few seconds. Here, we report that N. meningitidis type IV pili exploit the physical properties of host cells' plasma membranes to promote the formation of early tubular membrane structures essential for initial bacterial adhesion. These tubular structures, which form before any signaling events in host cells, concentrate and trap multiple plasma membrane-associated proteins in the vicinity of bacteria, thereby facilitating the selection, interaction and activation of specific adhesion and signaling receptors by bacterial ligands present on type IV pili. Our results define an additional paradigm for the recruitment of specific receptors by pathogenic bacteria, which depends on the physical property of bacterial pili to induce the formation of tubular plasma membrane structures enriched in integral plasma membrane receptors.

Despite the well-described association of skin lesions with Staphylococcus aureus, the distinct ability of clinical isolates to influence the local and systemic inflammatory response in a patient-specific manner is insufficiently characterized. In this study, we analyzed clinical recessive dystrophic epidermolysis bullosa (RDEB), which is characterized by wounds chronically colonized with S. aureus, to explore the relationship between inflammatory immune response and strain diversity. Children with RDEB (moderate phenotype, n = 5; severe phenotype, n = 10) and controls (n = 18) were enrolled in the study. Profiling of plasma proteins (n = 800), immune cells (n = 30 subsets and cytokine-producing cells), and cytokines (n = 38) identified a specific inflammatory signature in severe disease. Furthermore, patients with severe RDEB presented a high frequency of interleukin-17A+ (IL-17A+) cells among CD4+ and mucosal-associated invariant T (MAIT) lymphocytes. Positive S. aureus cultures from the skin of patients with RDEB allowed whole-genome sequencing of patient strains and assessment of primary keratinocyte immune response upon bacterial challenge. S. aureus secretome and conditioned medium from keratinocytes challenged with S. aureus strains from patients with severe but not from those with moderate RDEB promoted strong activation and a pro-IL-17 response in both CD4+ and MAIT cells. Our findings show that S. aureus strains isolated from patients with severe RDEB induce an IL-17-skewed immune response and pave the way for precision microbiology to explain and predict the highly variable virulence potential of bacterial clinical isolates.

Filamentous phages belong to Inoviruses, a family of non-lytic phages that are mutually beneficial to their bacterial hosts. These phages have a role in bacterial dissemination, biofilm formation or immune evasion. In Neisseria meningitidis, the strains harbouring the MDA filamentous phage are associated with invasive diseases through the MDAΦ key role in epithelial cell colonisation. Using MDAΦ and N. meningitidis as model organisms, we aimed to understand the relationship between filamentous phage infection, type IV pili antigenic variation and bacterial colonisation. The paradigm of filamentous phage infection has been defined for the phages Ff and CTX, where binding to the tips of bacterial type IV pili is a means of infecting their bacterial host. In contrast, we showed that MDAΦ binds N. meningitidis type IV pili along the length of the filament, rather than at the tip, with preferential binding to positively charged variants of PilE (the major fibre-forming pilin) demonstrating a role for antigenic variation in phage infection. Strikingly, bacteria expressing the more positively charged PilE were the most adhesive, meaning that MDAΦ primarily target the most adhesive bacteria. Finally, we showed that adhesion to human cells is sufficient to amplify the phage-positive meningococcal population. Taken together, this study reveals how the propagation strategy of a filamentous phage, aimed at selecting the best coloniser as a host, can promote the selection of hyperadhesive bacterial variants, linking phage infection to bacterial virulence.

Objectives:The aim of this study was to evaluate the contribution of metagenomic next-generation sequencing (mNGS) in critically ill patients with encephalitis of unknown etiology. Methods:This retrospective study (2016-2023) was conducted in a tertiary care referral neuro-ICU at La Pitié-Salpêtrière Hospital (Paris, France). The inclusion criteria were encephalitis with unknown etiology and mNGS performed on CSF, brain biopsy, and/or autopsy. We assessed the yield of mNGS and whether specific treatments were initiated. Neurologic outcome at 1 year was assessed using the Glasgow Outcome Scale-Extended (GOSE-1: death; GOSE-8: upper good recovery). Results:A total of 49 patients were included, of whom 44.9% were immunosuppressed. At 1 year, 38.8% had a GOSE score 4-8 and 47.7% died. mNGS was performed on the CSF of 40 of 49 patients (81.6%) and on brain biopsy of 19 of 49 patients (38.8%), including 12 patients who underwent both CSF and biopsy testing. Among the 40 mNGS analyses performed on the CSF, 7 (17.5%) yielded positive results but only 1 (2.5%) was likely causative. Conversely, 7 of 19 mNGS analyses (36.8%) on biopsies were positive and causative. Regarding the yield of mNGS in the entire cohort, 15 of 49 patients (30.6%) had a positive result but only 7 of 49 (14.3%) were causative (dengue virus, measles virus, rubella virus, Nocardia spp, HHV6, astrovirus, and orthobunyavirus), all from brain biopsies of immunocompromised patients. Conversely, 8 of 49 mNGS analyses (16.3%) were noncausative (polyomavirus, HHV8, HHV7, EBV, 2 pegiviruses, and 2 rhinoviruses). Specific treatments were initiated in 4 of 7 patients (57%). Among the 34 patients with a negative mNGS result, 5 (14.7%) were diagnosed with infectious encephalitis using conventional methods. Conclusion:In critically ill patients with encephalitis of unknown etiology, mNGS performed on brain biopsy could reduce diagnostic uncertainty.

Filamentous phages are non-lytic phages mutually beneficial to their bacterial hosts. In Neisseria meningitidis, the filamentous phage MDA is associated with invasive diseases thanks to its key role in the formation of biofilm during epithelium colonisation. The infection model for filamentous phages has been defined for phages Ff and CTX. These phages bind to the tips of bacterial pili before being translocated into the periplasm of their hosts. The aim of this study is to investigate the relationship between filamentous phage infection and type IV pili, using the bacterium Neisseria meningitidis and the bacteriophage MDA as model organisms. We show that MDAΦ rather binds to type IV pili along their entire length with preferential binding to positively charged variants of the major fibre-forming pilin, demonstrating a role for antigenic variation in phage infection. Strikingly, bacteria expressing the more positively charged pilin are also the most adhesive, suggesting that MDAΦ primarily target the most adhesive bacteria. Finally, we show that adhesion to human cells is sufficient to amplify the phage-positive meningococcal population. Overall, this study reveals how a filamentous phage can target hyperadhesive bacterial variants and promote their selection, thereby establishing a link between phage infection and bacterial colonisation.

We identified a novel human circovirus in an immunocompromised 66-year-old woman with sudden onset of self-limiting hepatitis. We detected human circovirus 1 (HCirV-1) transcripts in hepatocytes and the HCirV-1 genome long-term in the patient’s blood, stool, and urine. HCirV-1 is an emerging human pathogen that persists in susceptible patients.

Bacterial pathogens adapt and replicate within host cells, while host cells develop mechanisms to eliminate them. Using a dual proteomic approach, we characterized the intra-macrophage proteome of the facultative intracellular pathogen, Francisella novicida. More than 900 Francisella proteins were identified in infected macrophages after a 10-h infection. Biotin biosynthesis-related proteins were upregulated, emphasizing the role of biotin-associated genes in Francisella replication. Conversely, proteins encoded by the Francisella pathogenicity island (FPI) were downregulated, supporting the importance of the F. tularensis Type VI Secretion System for vacuole escape, not cytosolic replication. In the host cell, over 300 proteins showed differential expression among the 6200 identified during infection. The most upregulated host protein was cis-aconitate decarboxylase IRG1, known for itaconate production with antimicrobial properties in Francisella. Surprisingly, disrupting IRG1 expression did not impact Francisella's intracellular life cycle, suggesting redundancy with other immune proteins or inclusion in larger complexes. Over-representation analysis highlighted cell-cell contact and actin polymerization in macrophage deregulated proteins. Using flow cytometry and live cell imaging, we demonstrated that merocytophagy involves diverse cell-to-cell contacts and actin polymerization-dependent processes. These findings lay the groundwork for further exploration of merocytophagy and its molecular mechanisms in future research.Data are available via ProteomeXchange with identifier PXD035145.

The efficient transformation of Neisseria meningitidis and Neisseria gonorrhoeae facilitates the rapid construction of bacterial mutants with insertion of antibiotic resistance cassettes. However, this strategy limits the construction of strains with multiple mutations. Recent advances in markerless strategies for Neisseria species have enabled the construction of mutants without antibiotic resistance markers. However, these innovative approaches have potential limitations related to the selection strategy or the possible occurrence of spontaneous mutations in the selection marker genes. In addition, complementation tools or labelling strategies for N. meningitidis are also lacking. In this study, we have introduced new tools for markerless mutation, genetic complementation and labelling in N. meningitidis , thus improving the research possibilities for understanding and tackling these pathogens. ### Competing Interest Statement The authors have declared no competing interest.

Phototherapy is a low-risk alternative to traditional antibiotics against drug-resistant bacterial infections. However, optimizing phototherapy agents, refining treatment conditions, and addressing misuse of agents, remain a formidable challenge. This study introduces a novel concept leveraging the unique customizability of metal-organic frameworks (MOFs) to house size-matched dye molecules in “single rooms”. The mesoporous iron(III) carboxylate nanoMOF, MIL-100(Fe), and the hydrophobic heptamethine cyanine photothermal dye (Cy7), IR775, are selected as model systems. Their combination is predicted to minimize dye-dye interactions, leading to exceptional photostability and efficient light-to-heat conversion. Furthermore, MIL-100(Fe) preserves the antimicrobial nature of hydrophobic IR775, enabling it to disrupt bacterial cell envelopes. Through electrospinning, MIL-100(Fe)@IR775 nanoparticles are shaped into a gelatin-based film dressing for the treatment of skin wounds infected by Methicillin-resistant Staphylococcus aureus (MRSA). Activation of the dressing requires only a portable near-infrared light-emitting diode (NIR LED) and induces both low-dose photodynamic therapy (LPDT) and mild-temperature photothermal therapy (MPTT). Combined with the antimicrobial properties of IR775 and ferroptosis-like lipid peroxidation induced by MIL-100(Fe), the photoactive dressing eradicates MRSA and the healing is as quick as the uninfected wounds. This safe, cost-effective, and multifunctional therapeutic wound dressing offers a promising solution to overcome the current bottleneck in phototherapy.

The efficient natural transformation of Neisseria meningitidis allows the rapid construction of bacterial mutants in which the genes of interest are interrupted or replaced by antibiotic-resistance cassettes. However, this proved to be a double-edged sword, i.e., although facilitating the genetic characterization of this important human pathogen, it has limited the development of strategies for constructing markerless mutants without antibiotic-resistance markers. In addition, efficient tools for complementation or labeling are also lacking in N. meningitidis. In this study, we significantly expand the meningococcal genetic toolbox by developing new and efficient tools for the construction of markerless mutants (using a dual counterselection strategy), genetic complementation (using integrative vectors), and cell labeling (using a self-labeling protein tag). This expanded toolbox paves the way for more in-depth genetic characterization of N. meningitidis and might also be useful in other Neisseria species. IMPORTANCE Neisseria meningitidis and Neisseria gonorrhoeae are two important human pathogens. Research focusing on these bacteria requires genetic engineering, which is facilitated by their natural ability to undergo transformation. However, the ease of mutant engineering has led the Neisseria community to neglect the development of more sophisticated tools for gene editing, particularly for N. meningitidis. In this study, we have significantly expanded the meningococcal genetic toolbox by developing novel and efficient tools for markerless mutant construction, genetic complementation, and cell tagging. This expanded toolbox paves the way for more in-depth genetic characterization of N. meningitidis and might also be useful in other Neisseria species.

BACKGROUND:Allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are potentially curative treatments for severe combined immunodeficiency (SCID). Late-onset posttreatment manifestations (such as persistent hepatitis) are not uncommon. OBJECTIVE:We sought to characterize the prevalence and pathophysiology of persistent hepatitis in transplanted SCID patients (SCIDH+) and to evaluate risk factors and treatments. METHODS:We used various techniques (including pathology assessments, metagenomics, single-cell transcriptomics, and cytometry by time of flight) to perform an in-depth study of different tissues from patients in the SCIDH+ group and corresponding asymptomatic similarly transplanted SCID patients without hepatitis (SCIDH-). RESULTS:Eleven patients developed persistent hepatitis (median of 6 years after HSCT or GT). This condition was associated with the chronic detection of enteric viruses (human Aichi virus, norovirus, and sapovirus) in liver and/or stools, which were not found in stools from the SCIDH- group (n = 12). Multiomics analysis identified an expansion of effector memory CD8+ T cells with high type I and II interferon signatures. Hepatitis was associated with absence of myeloablation during conditioning, split chimerism, and defective B-cell function, representing 25% of the 44 patients with SCID having these characteristics. Partially myeloablative retransplantation or GT of patients with this condition (which we have named as "enteric virus infection associated with hepatitis") led to the reconstitution of T- and B-cell immunity and remission of hepatitis in 5 patients, concomitantly with viral clearance. CONCLUSIONS:Enteric virus infection associated with hepatitis is related to chronic enteric viral infection and immune dysregulation and is an important risk for transplanted SCID patients with defective B-cell function.

Differentiation between Whipple disease (WD) patients and patients carrying Tropheryma whipplei but suffering from disease other than WD (“carriers”) remains complex. We aimed to evaluate T. whipplei PCR among patients with WD and carriers in a large cohort at our referral clinical microbiology laboratory. This is an observational retrospective cohort study, including all patients between 2008 and 2020 with at least one positive result for T. whipplei using the real-time PCR RealCycler TRWH-UX kit. A total of 233 patients were included: 197 were considered carriers, and 36 had WD.

ABSTRACT Background Renal arcuate vein thrombosis (RAVT) is a rare and recently recognized cause of acute kidney injury (AKI) in young adults. However, the precise incidence and underlying pathophysiologic mechanisms leading to AKI in these patients remain elusive. Methods This study included all patients who underwent a kidney biopsy over a 40-month period sent to the pathology department of Necker-Enfants Malades Hospital, with evidence of RAVT. We performed coagulation tests, genetic testing for thrombophilia, complete urine toxicologic screening and kidney metagenomic sequencing to identify an underlying cause of thrombosis. Results We report five pediatric cases of RAVT discovered on kidney biopsy performed in the setting of unexplained AKI. Investigations did not reveal an underlying cause of thrombosis but only a significant nonsteroidal anti-inflammatory drugs (NSAIDs) use was reported in 4/5 patients, supporting a potential link between NSAIDs use and RAVT. By performing metagenomic sequencing on kidney biopsy samples, we detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the kidney of one patient. These results suggest that systemic SARS-CoV-2 infection may also be a key contributing factor of renal thrombosis, particularly by inducing potential endothelial disruption. Conclusions In conclusion, RAVT-induced AKI appears to be a multiple hit–mediated disease in which NSAIDs consumption and viral infection such as SARS-CoV-2 may be crucial contributing factors. These findings may have significant public health implications given the prevalence of NSAIDs use in the general population. Increased awareness and additional study of future cases may lead to a better understanding of this rare cause of AKI in children and young adults.

Ultrasound in Obstetrics & GynecologyVolume 61, Issue 1 p. 116-117 Letter to the Editor Fetal Zika virus infection diagnosed by metagenomic next-generation sequencing of amniotic fluid J. Fourgeaud, Corresponding Author J. Fourgeaud [email protected] orcid.org/0000-0003-3631-184X Université Paris Cité, FETUS, Paris, France Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, France J.F., B.R. and H.F. contributed equally to this work.Correspondence. (e-mail: [email protected])Search for more papers by this authorB. Regnault, B. Regnault Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, France J.F., B.R. and H.F. contributed equally to this work.Search for more papers by this authorH. Faury, H. Faury Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, France J.F., B.R. and H.F. contributed equally to this work.Search for more papers by this authorN. Da Rocha, N. Da Rocha Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, FranceSearch for more papers by this authorA. Jamet, A. Jamet Université Paris Cité, FETUS, Paris, France Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, France Institut Necker–Enfants Malades, INSERM U1151, CNRS UMR, 8253 Paris, FranceSearch for more papers by this authorJ. Stirnemann, J. Stirnemann Université Paris Cité, FETUS, Paris, France Department of Obstetrics and Fetal Therapy, Necker–Enfants Malades Hospital, AP–HP, Paris, FranceSearch for more papers by this authorM. Eloit, M. Eloit Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, FranceSearch for more papers by this authorP. Perot, P. Perot orcid.org/0000-0002-5194-8200 Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, FranceSearch for more papers by this authorM. Leruez-Ville, M. Leruez-Ville Université Paris Cité, FETUS, Paris, France Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, FranceSearch for more papers by this authorM. Driessen, M. Driessen Department of Obstetrics and Fetal Therapy, Necker–Enfants Malades Hospital, AP–HP, Paris, FranceSearch for more papers by this authorCollaborators, CollaboratorsSearch for more papers by this author J. Fourgeaud, Corresponding Author J. Fourgeaud [email protected] orcid.org/0000-0003-3631-184X Université Paris Cité, FETUS, Paris, France Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, France J.F., B.R. and H.F. contributed equally to this work.Correspondence. (e-mail: [email protected])Search for more papers by this authorB. Regnault, B. Regnault Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, France J.F., B.R. and H.F. contributed equally to this work.Search for more papers by this authorH. Faury, H. Faury Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, France J.F., B.R. and H.F. contributed equally to this work.Search for more papers by this authorN. Da Rocha, N. Da Rocha Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, FranceSearch for more papers by this authorA. Jamet, A. Jamet Université Paris Cité, FETUS, Paris, France Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, France Institut Necker–Enfants Malades, INSERM U1151, CNRS UMR, 8253 Paris, FranceSearch for more papers by this authorJ. Stirnemann, J. Stirnemann Université Paris Cité, FETUS, Paris, France Department of Obstetrics and Fetal Therapy, Necker–Enfants Malades Hospital, AP–HP, Paris, FranceSearch for more papers by this authorM. Eloit, M. Eloit Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, FranceSearch for more papers by this authorP. Perot, P. Perot orcid.org/0000-0002-5194-8200 Pathogen Discovery Laboratory, Institut Pasteur, Université de Paris, Paris, FranceSearch for more papers by this authorM. Leruez-Ville, M. Leruez-Ville Université Paris Cité, FETUS, Paris, France Department of Clinical Microbiology, Necker–Enfants Malades Hospital, AP–HP, Paris, FranceSearch for more papers by this authorM. Driessen, M. Driessen Department of Obstetrics and Fetal Therapy, Necker–Enfants Malades Hospital, AP–HP, Paris, FranceSearch for more papers by this authorCollaborators, CollaboratorsSearch for more papers by this author First published: 14 September 2022 https://doi.org/10.1002/uog.26074 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Open Research DATA AVAILABILITY STATEMENT Data sharing not applicable to this article as no datasets were generated or analysed during the current study Supporting Information Filename Description uog26074-sup-0001-Supinfo.docxWord 2007 document , 18.2 KB Appendix S1 Methodology for metagenomic next-generation sequencing and Zika virus reverse-transcription polymerase chain reaction and serology Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1Mercado M, Ailes EC, Daza M, Tong VT, Osorio J, Valencia D, Rico A, Galang RR, González M, Ricaldi JN, Anderson KN, Kamal N, Thomas JD, Villanueva J, Burkel VK, Meaney-Delman D, Gilboa SM, Honein MA, Jamieson DJ, Ospina ML. Zika virus detection in amniotic fluid and Zika-associated birth defects. Am J Obstet Gynecol 2020; 222: 610. e1–13. 2Schaub B, Vouga M, Najioullah F, Gueneret M, Monthieux A, Harte C, Muller F, Jolivet E, Adenet C, Dreux S, Leparc-Goffart I, Cesaire R, Volumenie JL, Baud D. Analysis of blood from Zika virus-infected fetuses: a prospective case series. Lancet Infect Dis 2017; 17: 520–527. 3Durand GA, Piorkowski G, Thirion L, Ninove L, Giron S, Zandotti C, Denis J, Badaut C, Failloux AB, Grard G, Leparc-Goffart I, de Lamballerie X. Vector-borne transmission of the Zika virus Asian genotype in Europe. Viruses 2020; 12: 296. 4Eldin C, Ninove L, Drouet H, Gautret P, Leparc-Goffart I, Parola P. Dengue fever type 1 in five travellers returning from the Comoros Islands to Marseille in August 2019 - The risk of importation and subsequent autochthonous dengue transmission in France. Travel Med Infect Dis 2020; 33: 101507. Volume61, Issue1January 2023Pages 116-117 ReferencesRelatedInformation

Using metagenomic next-generation sequencing and reverse-transcription polymerase chain reaction, we detected the Aichi virus genome in tissues of patients with primary immune deficiency and unexplained multiorgan inflammatory involvement. We showed evidence supporting the causality of Aichi virus in these cases. Background Metagenomic next-generation sequencing (mNGS) was used to assess patients with primary or secondary immune deficiencies (PIDs and SIDs) who presented with immunopathological conditions related to immunodysregulation. Methods Thirty patients with PIDs or SIDs who presented with symptoms related to immunodysregulation and 59 asymptomatic patients with similar PIDs or SIDs were enrolled. mNGS was performed on organ biopsy. Specific Aichi virus (AiV) reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm AiV infection and screen the other patients. In situ hybridization (ISH) assay was done on AiV-infected organs to identify infected cells. Virus genotype was determined by phylogenetic analysis. Results AiV sequences were detected using mNGS in tissue samples of 5 patients and by RT-PCR in peripheral samples of another patient, all of whom presented with PID and long-lasting multiorgan involvement, including hepatitis, splenomegaly, and nephritis in 4 patients. CD8+ T-cell infiltration was a hallmark of the disease. RT-PCR detected intermittent low viral loads in urine and plasma from infected patients but not from uninfected patients. Viral detection stopped after immune reconstitution obtained by hematopoietic stem cell transplantation. ISH demonstrated the presence of AiV RNA in hepatocytes (n = 1) and spleen tissue (n = 2). AiV belonged to genotype A (n = 2) or B (n = 3). Conclusions The similarity of the clinical presentation, the detection of AiV in a subgroup of patients suffering from immunodysregulation, the absence of AiV in asymptomatic patients, the detection of viral genome in infected organs by ISH, and the reversibility of symptoms after treatment argue for AiV causality.

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (1010 genome copies/mL) in January 2022. In March 2022, we found >108 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.

Staphylococcus aureus is a predominant cause of chronic lung infections. While the airway environment is rich in highly sialylated mucins, the interaction of S. aureus with sialic acid is poorly characterized. Using S. aureus USA300 as well as clinical isolates, we demonstrate that quorum-sensing dysfunction, a hallmark of S. aureus adaptation, correlates with a greater ability to consume free sialic acid, providing a growth advantage in an air-liquid interface model and in vivo. Furthermore, RNA-seq experiment reveals that free sialic acid triggers transcriptional reprogramming promoting S. aureus chronic lifestyle. To support the clinical relevance of our results, we show the co-occurrence of S. aureus , sialidase-producing microbiota and free sialic acid in the airway of patients with cystic fibrosis. Our findings suggest a dual role for sialic acid in S. aureus airway infection, triggering virulence reprogramming and driving S. aureus adaptive strategies through the selection of quorum-sensing dysfunctional strains.