Unlabelled: Intestinal microsporidiosis caused by is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication.
View Article and Find Full Text PDFInfluenza A viruses are responsible for human seasonal epidemics and severe animal pandemics with a risk of zoonotic transmission to humans. The viral segmented RNA genome is encapsidated by nucleoproteins (NP) and attached to the heterotrimeric polymerase, forming the viral ribonucleoproteins (vRNPs). Flexible helical vRNPs are central for viral transcription and replication.
View Article and Find Full Text PDFBackground: The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC.
View Article and Find Full Text PDFInfluenza viruses transcribe and replicate their genome in the nucleus of the infected cells, two functions that are supported by the viral RNA-dependent RNA-polymerase (FluPol). FluPol displays structural flexibility related to distinct functional states, from an inactive form to conformations competent for replication and transcription. FluPol machinery is constituted by a structurally-invariant core comprising the PB1 subunit stabilized with PA and PB2 domains, whereas the PA endonuclease and PB2 C-domains can pack in different configurations around the core.
View Article and Find Full Text PDFIntroduction: Rituximab is a first-line treatment for membranous nephropathy. Nephrotic syndrome limits rituximab exposure due to urinary drug loss. Rituximab underdosing (serum level <2 μg/ml at month-3) is a risk factor for treatment failure.
View Article and Find Full Text PDFInfluenza virus genome encapsidation is essential for the formation of a helical viral ribonucleoprotein (vRNP) complex composed of nucleoproteins (NP), the trimeric polymerase, and the viral genome. Although low-resolution vRNP structures are available, it remains unclear how the viral RNA is encapsidated and how NPs assemble into the helical filament specific of influenza vRNPs. In this study, we established a biological tool, the RNP-like particles assembled from recombinant influenza A virus NP and synthetic RNA, and we present the first subnanometric cryo-electron microscopy structure of the helical NP-RNA complex (8.
View Article and Find Full Text PDFIntroduction: Kidney transplant recipients (KTRs) have an increased risk of cardiovascular (CV) events (CVEs) compared with the general population. The impact of insulin resistance on CV risk after transplantation is not well defined.
Methods: We tested whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, may predict posttransplant CVEs in a cohort of 715 consecutive KTRs all included 1 year after transplant.
For 30 years, photopheresis is used to treat graft versus host disease and heart or lung allograft rejection. In this review, we discuss the place of photopheresis in kidney transplantation both in prevention or treatment of rejection. Mechanisms of action in kidney transplantation are mainly based on results observed in graft versus host disease and in heart or lung transplantation.
View Article and Find Full Text PDFAdaptation of avian influenza RNA polymerase (FluPol) to human cells requires mutations on the 627-NLS domains of the PB2 subunit. The E627K adaptive mutation compensates a 33-amino-acid deletion in the acidic intrinsically disordered domain of the host transcription regulator ANP32A, a deletion that restricts FluPol activity in mammalian cells. The function of ANP32A in the replication transcription complex and in particular its role in host restriction remains poorly understood.
View Article and Find Full Text PDFIn recent years, cryo-electron microscopy (cryo-EM) has emerged as an important standalone technique within structural biology [...
View Article and Find Full Text PDFBackground: Interstitial inflammation and peritubular capillaritis are observed in many diseases on native and transplant kidney biopsies. A precise and automated evaluation of these histological criteria could help stratify patients' kidney prognoses and facilitate therapeutic management.
Methods: We used a convolutional neural network to evaluate those criteria on kidney biopsies.
Rationale & Objective: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients.
View Article and Find Full Text PDFNephrol Dial Transplant
June 2023
Introduction: Adverse events (AEs) of immune checkpoint inhibitors (ICIs) are frequent and mainly due to an overactivity of the immune system leading to excessive inflammatory responses (immune-related AE) that can affect any organ of the body. Beside the most frequent AEs, there are rare AEs whose diagnosis and treatment can be challenging. We report here a singular case of capillary leak syndrome (CLS) associated with chylothorax occurring in a patient who has been treated with adjuvant nivolumab (anti-PD1) for resected AJCC stage IIB primary melanoma.
View Article and Find Full Text PDFDetermining the structural organisation of viral replication complexes and unravelling the impact of infection on cellular homeostasis represent important challenges in virology. This may prove particularly useful when confronted with viruses that pose a significant threat to human health, that appear unique within their family, or for which knowledge is scarce. Among , bornaviruses (family ) stand out due to their compact genomes and their nuclear localisation for replication.
View Article and Find Full Text PDFCryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France.
View Article and Find Full Text PDFInfluenza virus infection causes considerable morbidity and mortality, but current therapies have limited efficacy. We hypothesized that investigating the metabolic signaling during infection may help to design innovative antiviral approaches. Using bronchoalveolar lavages of infected mice, we here demonstrate that influenza virus induces a major reprogramming of lung metabolism.
View Article and Find Full Text PDFThe development of safe and effective vaccines in a record time after the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a remarkable achievement, partly based on the experience gained from multiple viral outbreaks in the past decades. However, the Coronavirus Disease 2019 (COVID-19) crisis also revealed weaknesses in the global pandemic response and large gaps that remain in our knowledge of the biology of coronaviruses (CoVs) and influenza viruses, the 2 major respiratory viruses with pandemic potential. Here, we review current knowns and unknowns of influenza viruses and CoVs, and we highlight common research challenges they pose in 3 areas: the mechanisms of viral emergence and adaptation to humans, the physiological and molecular determinants of disease severity, and the development of control strategies.
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