BACKGROUND: Preeclampsia (PE) affects 2–8% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality. In high-risk pregnant women, low-dose aspirin (LDA 100—160 mg/day) started before 16 WG reduces the incidence of PE, prematurity, perinatal mortality and low birth weight. First trimester screening of PE allows the identification of a population of pregnant women at high risk of early onset PE and perinatal mortality. It remains unclear whether, on a population scale, the systematic implementation of first trimester screening of PE with treatment of high-risk patients by LDA leads to an improvement of maternal and perinatal health. METHODS: This multicenter open randomized controlled trial with two parallel groups will include 14,500 pregnant women between 11–14 WG. Eligible women agreeing to participate in the trial will be randomized either to the experimental group with management including screening of PE, or to the control group with usual care without screening of PE. For women in the screening group, the risk of PE will be calculated according to an algorithm combining clinical characteristics, uterine arteries Doppler profile and PlGF concentration. Women with a positive screening test (i.e. predicted risk > 1/100) will receive aspirin at 160 mg/day. For women with negative screening, usual pregnancy monitoring without aspirin will be offered. The primary outcome is a composite of severe perinatal morbidity including at least one of the following: perinatal mortality, birth before 34 WG and birth weight < 3rd centile. Secondary endpoints include maternal morbidity and mental health outcomes, and a cost-effectiveness evaluation. This study will have a 90% power to show a 50% reduction of the primary outcome in at-risk women, expected to represent 10% of the total population in each group, i.e. an overall expected 3% frequency of the primary outcome in the intervention group as a whole versus 4% in the control group. DISCUSSION: This large multicenter randomized trial aims to determine with adequate power if the implementation of first trimester PE screening in all pregnant women would decrease the incidence of perinatal mortality, prematurity before 34 WG and birth weight < 3rd centile. TRIAL REGISTRATION: ClinicalTrials.gov NCT 05521776 (August 30, 2022).

Ventilator-associated pneumonia (VAP) is a significant complication in mechanically ventilated patients. Paradoxically, it lacks precise diagnostic criteria, making the identification of a reliable diagnostic indicator an unmet medical need. Lipids are critical regulators of innate lung defense. The aim of the study was to identify lipid alterations specific to VAP in tracheal aspirates of patients with ARDS. Tracheal aspirates samples from ventilated patients were collected longitudinally from patients with COVID-19-related ARDS. Tracheal aspirates sampled at the day of VAP diagnosis were used to assess VAP specific lipidome and were compared with matched controls (patients without VAP). Lipid detection was performed using ultra-high-performance liquid chromatography with high resolution mass spectrometry. The statistical analysis included: unsupervised multivariate methods, partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares discriminant analysis (OPLS-DA), and the area under the receiver operating characteristic (AUROC) curve to assess classification performance. The Benjamini–Hochberg adjusted p-value was used to control the false discovery rate. We studied 39 patients (26 VAP and 13 control patients). The characteristics of VAP and control patients were similar, including biological markers such as neutrophils, CRP, and PCT. The lipid signature, composed of 272 lipids, differed between VAP and control patients (p = 0.003). Phosphatidylcholines were the most represented with 17 significantly upregulated and 6 downregulated lipids. OPLSDA identified 8 best candidates as VAP biomarkers with sphingomyelin (34:1) and phosphatidylcholine (O-34:1) presenting the best scores (AUROC = 0.85 [0.71–0.95] and 0.83 [0.66–0.94], respectively). Combinations of several lipid biomarkers did not improve the prediction accuracy. During ARDS, lung lipidome mostly resulted in breakdown product of host–pathogen interactions (surfactant and pulmonary cells). We investigated VAP-specific lipids in tracheal aspirate and identified significant alterations in lipidomic profiles, likely driven by active infection dynamic and the breakdown of surfactant and pulmonary cells. Among the potential VAP biomarker candidates in COVID-19 ARDS, sphingomyelin (34:1) and phosphatidylcholine (O-34:1) demonstrated predictive performance for VAP that surpassed all previously tested biomarkers.

Subsets of multiple myeloma (MM) and monoclonal gammopathies of undetermined significance (MGUS) present with a monoclonal immunoglobulin specific for hepatitis C virus (HCV), thus are presumably HCV-driven, and antiviral treatment can lead to the disappearance of antigen stimulation and improved control of clonal plasma cells. Here we studied the role of hepatitis B virus (HBV) in the pathogenesis of MGUS and MM in 45 HBV-infected patients with monoclonal gammopathy. We analyzed the specificity of recognition of the monoclonal immunoglobulin of these patients and validated the efficacy of antiviral treatment (AVT). For 18 of 45 (40%) HBV-infected patients, the target of the monoclonal immunoglobulin was identified: the most frequent target was HBV (n=11), followed by other infectious pathogens (n=6) and glucosylsphingosine (n=1). Two patients whose monoclonal immunoglobulin targeted HBV (HBx and HBcAg), implying that their gammopathy was HBV-driven, received AVT and the gammopathy did not progress. AVT efficacy was then investigated in a large cohort of HBV-infected MM patients (n=1367) who received or did not receive anti-HBV treatments and compared to a cohort of HCV-infected MM patients (n=1220). AVT significantly improved patient probability of overall survival (P=0.016 for the HBV-positive cohort, P=0.005 for the HCV-positive cohort). Altogether, MGUS and MM disease can be HBV- or HCV-driven in infected patients, and the study demonstrates the importance of AVT in such patients.

ABSTRACT:The pathophysiology of primary burning mouth syndrome (BMS) remains controversial. Targeted analyses or "omics" approach of saliva provide diagnostic or pathophysiological biomarkers. This pilot study's primary objective was to explore the pathophysiology of BMS through a comparative analysis of the salivary metabolome among 26 BMS female cases and 25 age- and sex-matched control subjects. Secondary objectives included comparative analyses of inflammatory cytokines, neuroinflammatory markers, and steroid hormones among cases and control subjects, and among BMS patients according to their clinical characteristics. Salivary metabolome, neuroinflammatory markers, cytokines, and steroids were, respectively, analysed by liquid chromatography coupled with mass spectrometry, ELISA and protease activity assay, and multiparametric Luminex method. Among the 166 detected metabolites, univariate analysis did not find any discriminant metabolite between groups. Supervised multivariate analysis divided patients into 2 groups with an accuracy of 60% but did not allow significant discrimination (permutation test, P = 0.35). Among the metabolites contributing to the model, 3 belonging to the tyrosine pathway ( l -dopa, l -tyrosine, and tyramine) were involved in the discrimination between cases and control subjects, and among BMS patients according to their levels of pain. Among the detectable molecules, levels of cytokines, steroid hormones, and neuroinflammatory markers did not differ between cases and control subjects and were not associated with characteristics of BMS patients. These results do not support the involvement of steroid hormones, inflammatory cytokines, or inflammatory neurogenic mediators in the pathophysiology of pain in BMS, whereas the observed shift in tyrosine metabolism may indicate an adaptative response to chronic pain or an impaired dopaminergic transmission.

Central nervous system (CNS) barrier impairment has been reported in amyotrophic lateral sclerosis (ALS), highlighting its potential significance in the disease. In this context, we aim to shed light on its involvement in the disease, by determining albumin quotient (QAlb) at the time of diagnosis of ALS in a large cohort of patients. Patients from the university hospital of Tours (n = 307) were included in this monocentric, retrospective study. In total, 92 patients (30%) had elevated QAlb levels. This percentage was higher in males (43%) than in females (15%). Interestingly, QAlb was not associated with age of onset, age at sampling or diagnostic delay. However, we found an association with ALS functional rating scale-revised (ALSFRS-r) at diagnosis but this was significant only in males. The QAlb levels were not linked to the presence of a pathogenic mutation. Finally, we performed a multivariate survival analysis and found that QAlb was significantly associated with survival in male patients (HR = 2.3, 95% CI = 1.2–4.3, p = 0.009). A longitudinal evaluation of markers of barrier impairment, in combination with inflammatory biomarkers, could give insight into the involvement of CNS barrier impairment in the pathogenesis of the disease. The gender difference might guide the development of new drugs and help personalise the treatment of ALS.

A 16-year-old child with no medical history was admitted to the hospital emergency for abdominal pain associated with polyuria-polydipsia and weight loss (baseline BMI: 25,4 kg/m2). Diagnosis of severe ketoacidosis was quickly raised regarding major metabolic acidosis, high ketonemia and glycemia. Acute pancreatitis was then diagnosed according to a plasmatic lipase more than tenfold normal values associated with a severe hypertriglyceridemia superior to 100 mmol/L. The triad composed of diabetic ketoacidosis-acute pancreatitis-hypertriglyceridemia is rarely found in childhood and can have deleterious consequences. The etiology of this disease is still enigmatic, as one can be both, cause and consequence of the other. Genetic investigation of familial chylomicronemia legitimated to invalidate the dyslipidemia etiology of this event. On the other hand, the association of a genetic variant of lipoprotein lipase leading to a decrease in its activity, with the insulinopenia of type 1 diabetes most certainly triggered this episode of hypertriglyceridemia.

Iron metabolism is tightly linked to infectious and inflammatory signals through hepcidin synthesis. To date, iron homeostasis during SARS-CoV-2 infection has not yet been described. The aim of this study is to characterize the hepcidin and erythroid regulators (growth differentiation factor 15 (GDF-15) and erythroferrone (ERFE)) by measuring concentrations in plasma in context of COVID-19 disease. We performed a single-center observational study of patients with COVID-19 to evaluate concentrations of main regulatory proteins involved in iron homeostasis, namely: hepcidin, ERFE and GDF-15. SARS-CoV-2 infection (COVID-19 + ) was defined by a positive RT-PCR. Sixteen patients with COVID-19 + were gender-matched and age-matched to 16 patients with a sepsis unrelated to SARS-CoV-2 (COVID-19 − ) and were compared with non-parametric statistic test. Clinical and hematological parameters, plasma iron, transferrin, transferrin saturation, ferritin, soluble transferrin receptor and C reactive protein were not statistically different between both groups. Median plasma hepcidin concentrations were higher in the COVID-19 + group (44.1 (IQR 16.55–70.48) vs 14.2 (IQR 5.95–18.98) nmol/L, p=0.003), while median ERFE and GDF-15 concentrations were lower in the COVID-19 + group (0.16 (IQR 0.01–0.73) vs 0.89 (IQR 0.19–3.82) ng/mL, p=0.035; 2003 (IQR 1355–2447) vs 4713 (IQR 2082–7774) pg/mL, p=0015), respectively) compared with the COVID-19 − group. This is the first study reporting lower ERFE and GDF-15 median concentrations in patients with COVID-19 + compared with patients with COVID-19 − , associated with an increased median concentration of hepcidin in the COVID-19 + group compared with COVID19 − group.

There is currently no diagnostic or prognostic biomarker available in clinical practice for Amyotrophic Lateral Sclerosis (ALS). The objective of this study was to monitor a combination of various inflammatory markers, lipids, and apolipoproteins alterations in ALS patients at the time of diagnosis, to assess their role as early diagnostic or prognostic biomarker candidates. C-reactive protein, orosomucoid, prealbumin, calprotectin, lipids and apolipro-teins were determined in the blood of all subjects (25 ALS patients, 23 controls) as routinely performed in our laboratory. Inflammatory mediators were evaluated by a bead-based multiplex assay. A two-step approach was used for each analytical strategy: univariate analysis followed by multivariate analysis. Eight features were sig-nificantly different between ALS patients and controls, sometimes with important fold changes. The supervised Partial least Squares Discriminant Analysis separated ALS and controls with great accuracy (94 %) and the per-mutation test was significant (p < 0.01), ensuring the robustness of the model. The prediction model leads to a mean sensitivity and specificity of 90 ( + /-10) and 78 ( + /-10) %, respectively, with a mean predictive positive value and negative predictive value of 80 ( + /-8.9) and 89 ( + /-11.8) %, respectively. However, the models did not discriminate subgroups of ALS patients based on ALS characteristics. This study highlights the usefulness of evaluating a combination of multiple pathways rather than focusing on a single target. These promising results suggest the need for the longitudinal monitoring of these candidates to determine their role in disease evolution.

A 16-year-old child with no medical history was admitted to the hospital emergency for abdominal pain associated with polyuria-polydipsia and weight loss (baseline BMI: 25,4 kg/m2). Diagnosis of severe ketoacidosis was quickly raised regarding major metabolic acidosis, high ketonemia and glycemia. Acute pancreatitis was then diagnosed according to a plasmatic lipase more than tenfold normal values associated with a severe hypertriglyceridemia superior to 100 mmol/L. The triad composed of diabetic ketoacidosis-acute pancreatitis-hypertriglyceridemia is rarely found in childhood and can have deleterious consequences. The etiology of this disease is still enigmatic, as one can be both, cause and consequence of the other. Genetic investigation of familial chylomicronemia legitimated to invalidate the dyslipidemia etiology of this event. On the other hand, the association of a genetic variant of lipoprotein lipase leading to a decrease in its activity, with the insulinopenia of type 1 diabetes most certainly triggered this episode of hypertriglyceridemia.Une jeune adolescente de 16 ans, sans antécédent médical, s'est présentée aux urgences pour douleurs abdominales dans un contexte de polyuro-polydipsie avec amaigrissement (IMC initial : 25,4 kg/m2). Une acidocétose sévère a rapidement été évoquée devant une acidose métabolique majeure, ainsi qu'une cétonémie et glycémie élevées. Une pancréatite aiguë a ensuite été diagnostiquée devant une lipase plasmatique supérieure à 10 fois les valeurs normales associée à une hypertriglycéridémie majeure de plus de 100 mmol/L. La triade acidocétose-pancréatite aiguë-hypertriglycéridémie est un phénomène très rarement retrouvé dans l'enfance et qui peut avoir des conséquences dramatiques. Il s'agit d'une pathologie à l'étiologie encore énigmatique, l'une pouvant être la cause et la conséquence de l'autre. L'exploration génétique d'une hyperchylomicronémie a pu permettre d'infirmer l'étiologie dyslipidémique de cet épisode. En revanche, l'association d'un variant génétique de la lipoprotéine lipase conduisant à une diminution de son activité, à l'insulinopénie du diabète de type 1 a très certainement déclenché cet épisode d'hypertriglycéridémie.

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

Phosphoinositides account for only a small proportion of cellular phospholipids, but have long been known to play an important role in diverse cellular processes, such as cell signaling, the establishment of organelle identity, and the regulation of cytoskeleton and membrane dynamics. As expected, given their pleiotropic regulatory functions, they have key functions in viral replication. The spatial restriction and steady-state levels of each phosphoinositide depend primarily on the concerted action of specific phosphoinositide kinases and phosphatases. This review focuses on a number of remarkable examples of viral strategies involving phosphoinositide kinases to ensure effective viral replication.

ObjectivesAnti-drug antibodies (ADA) are responsible for decreased adalimumab efficacy in axial spondyloarthritis (SpA). We aimed to evaluate the ability of methotrexate (MTX) to decrease adalimumab immunisation.MethodsA total of 110 patients eligible to receive adalimumab 40 mg subcutaneously (s.c.) every other week were randomised (1:1 ratio) to receive, 2 weeks before adalimumab (W-2) and weekly, MTX 10 mg s.c. (MTX+) or not (MTX−). ADA detection and adalimumab serum concentration were assessed at weeks 4 (W4), 8 (W8), 12 (W12) and 26 (W26) after starting adalimumab (W0). The primary outcome was the proportion of patients with ADA at W26. Four years after the study completion, we retrospectively analysed adalimumab maintenance in relation with MTX co-treatment duration.ResultsWe analysed data for 107 patients (MTX+; n=52; MTX-; n=55). ADA were detected at W26 in 39/107 (36.4%) patients: 13/52 (25%) in the MTX+ group and 26/55 (47.3%) in the MTX− group (p=0.03). Adalimumab concentration was significantly higher in the MTX+ than MTX− group at W4, W8, W12 and W26. The two groups did not differ in adverse events or efficacy. In the follow-up study, MTX co-treatment >W26 versus no MTX or ≤W26 was significantly associated with adalimumab long-term maintenance (p=0.04).ConclusionMTX reduces the immunogenicity and ameliorate the pharmacokinetics of adalimumab in axial SpA. A prolonged co-treatment of MTX>W26 seems to increase adalimumab long-term maintenance.

Previous studies showed that monoclonal immunoglobulins G (IgGs) of "monoclonal gammopathy of undetermined significance" (MGUS) and myeloma were hyposialylated, thus presumably pro-inflammatory, and for about half of patients, the target of the monoclonal IgG was either a virus-Epstein-Barr virus (EBV), other herpes viruses, hepatitis C virus (HCV)-or a glucolipid, lysoglucosylceramide (LGL1), suggesting antigen-driven disease in these patients. In the present study, we show that monoclonal IgAs share these characteristics. We collected 35 sera of patients with a monoclonal IgA (6 MGUS, 29 myeloma), and we were able to purify 25 of the 35 monoclonal IgAs (6 MGUS, 19 myeloma). Monoclonal IgAs from MGUS and myeloma patients were significantly less sialylated than IgAs from healthy volunteers. When purified monoclonal IgAs were tested against infectious pathogens and LGL1, five myeloma patients had a monoclonal IgA that specifically recognized viral proteins: the core protein of HCV in one case, EBV nuclear antigen 1 (EBNA-1) in four cases (21.1% of IgA myeloma). Monoclonal IgAs from three myeloma patients reacted against LGL1. In summary, monoclonal IgAs are hyposialylated and as described for IgG myeloma, significant subsets (8/19, or 42%) of patients with IgA myeloma may have viral or self (LGL1) antigen-driven disease.

PM specificity of Pr55 Gag membrane binding is mediated through the interaction of PI(4,5)P 2 with the matrix (MA) basic residues. It was shown that overexpression of a PI(4,5)P 2 -depleting enzyme strongly impaired PM localization of Pr55 Gag . However, cellular factors that control PI(4,5)P 2 production required for Pr55 Gag -PM targeting have not yet been characterized. In this study, by individually inhibiting PIP5K1 isoforms, we elucidated a correlation between PI(4,5)P 2 metabolism pathways mediated by PIP5K1 isoforms and the targeting of Pr55 Gag to the PM of TZM-bl HeLa cells. Confocal microscopy analyses of cells depleted from PIP5K1α and PIP5K1γ show a rerouting of Pr55 Gag to various intracellular compartments. Notably, Pr55 Gag is degraded by the proteasome and/or by the lysosomes in PIP5K1α-depleted cells, while Pr55 Gag is targeted to endosomal vesicles in PIP5K1γ-depleted cells. Thus, our results highlight, for the first time, the roles of PIP5K1α and PIP5K1γ as determinants of Pr55 Gag targeting to the PM.

: Chronic stimulation by infectious or self-antigens initiates subsets of monoclonal gammopathies of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). Recently, glucosylsphingosine (GlcSph) was reported to be the target of one third of monoclonal immunoglobulins (Igs). In this study of 233 patients (137 MGUS, 6 SMM, 90 MM), we analyzed the GlcSph-reactivity of monoclonal Igs and non-clonal Igs. The presence of GlcSph-reactive Igs in serum was unexpectedly frequent, detected for 103/233 (44.2%) patients. However, GlcSph was targeted by the patient's monoclonal Ig for only 37 patients (15.9%); for other patients (44 MGUS, 22 MM), the GlcSph-reactive Igs were non-clonal. Then, the characteristics of patients were examined: compared to MM with an Epstein-Barr virus EBNA-1-reactive monoclonal Ig, MM patients with a GlcSph-reactive monoclonal Ig had a mild presentation. The inflammation profiles of patients were similar except for moderately elevated levels of 4 cytokines for patients with GlcSph-reactive Igs. In summary, our study highlights the importance of analyzing clonal Igs separately from non-clonal Igs and shows that, if autoimmune responses to GlcSph are frequent in MGUS/SMM and MM, GlcSph presumably represents the initial pathogenic event for ~16% cases. Importantly, GlcSph-initiated MM appears to be a mild form of MM disease.

EJD, vol. 30, n◦ 4, July-August 2020 A 28-year-old man presented with a black nodule on his head. The diagnosis of WAS had been made clinically when the patient was four years old. The lesion had been noticed by the patient three months before. Physical examination revealed an 8×6-mm black nodule with a small ulceration in the centre at the crown of his head (figure 1A). Dermoscopy revealed an ulceration and large blue-grey ovoid nests in addition to arborizing vessels (figure 1B). Histopathological examination of the excised tumour showed tumour nests with melanin deposition in the superficial dermis, with a crust over the tumour (figure 1C). Some tumour nests were in contact with the epidermis (figure 1D); they were made of atypical, mitotic cells (figure 1F). The infiltrating cells around the tumour were rather sparse (figure 1E). These clinical, dermoscopic and histopathological findings led to the diagnosis of BCC. Immunohistochemistry revealed that the cells infiltrating the base of the tumour were CD4+/CD8+ T lymphocytes; no B lymphocytes were seen (figure 1G-I). Within the infiltration, CD56+ NK cells were sparse, but a substantial amount of infiltrating TIA1+/Granzyme B+ cells in those areas was seen (figure 1J-L). There was no relapse one year after resection of the tumour. WAS is a rare X-linked primary immunodeficiency characterized by deficiency in haematopoiesis and the immune system [3]. Defective functions of T cells include an impairment of proliferation in response to T-cell receptor (TCR) stimulation, secretion of cytokines and signalling under TCR [3, 4]. Furthermore, NK cells in WAS fail to form lytic synapses and express low levels of CD56, being occasionally completely CD56-negative [5]. To elucidate the profile of infiltrating cells around the tumour, we carried out an immunohistochemical analysis using, as a control, 10 BCCs from immunocompetent patients (see supplementary table 1). The pattern of infiltrating lymphocytes and NK cells is intriguing in terms of the immunological defects of WAS compared to the 10 BCC immunocompetent patients. Infiltrating CD8+ T lymphocytes were relatively abundant compared to infiltrating CD4+ T lymphocytes, in addition to the low number of infiltrating B lymphocytes in the WAS case compared to controls. Although a substantial number of infiltrating NK cells, shown by immunohistochemistry for TIA-1 and Granzyme B, were seen, the expression of CD56 was low in those cells. This pattern of NK cells was found in only 3/10 cases of BCC from immunocompetent patients. The exact mechanisms and functions of genes and/or proteins related to WAS in the skin remain to be elucidated. The accumulation of such cases may unravel the mechanisms of carcinogenesis via the immunodeficiency against tumours and will probably reveal why BCC is rare in WAS.

The poor diffusion of intravenous antibiotics in lung tissue makes nosocomial pneumonia challenging to treat, notably in critical patients under mechanical ventilation. The combination of ultrasound and microbubbles (USMB) is an emerging method for non-invasive and targeted enhancement of uptake of various drugs in several organs. This study aims to evaluate if USMB may increase amikacin concentration in condensed lung tissues in a mechanically ventilated rabbit model. When applied 60 or 160 min after the beginning of an intravenous amikacin infusion, USMB increased amikacin concentration in the condensed lung tissue by 1.33 (p = 0.025) or 1.56-fold (p = 0.028) respectively. When applied 70 min after the beginning of an intravenous amikacin infusion, USMB increased amikacin concentration in the muscle tissue by 2.52 (p = 0.025). In conclusion, this study demonstrates that USMB is a promising method for the targeted delivery of amikacin in mechanically ventilated condensed lung, thus opening new therapeutic fields against lung infections.

Hepatitis C virus (HCV) virions contain a subset of host liver cells proteome often composed of interesting virus-interacting factors. A proteomic analysis performed on double gradient-purified clinical HCV highlighted the translation regulator LARP1 on these virions. This finding was validated using post-virion capture and immunoelectron microscopy, as well as immunoprecipitation applied to in vitro (Huh7.5 liver cells) grown (Gt2a, JFH1 strain) and patient-derived (Gt1a) HCV particles. Upon HCV infection of Huh7.5 cells, we observed a drastic transfer of LARP1 to lipid droplets, inducing colocalization with core proteins. RNAi-mediated depletion of LARP1 using the C911 control approach decreased extracellular infectivity of HCV Gt1a (H77), Gt2a (JFH1), and Gt3a (S52 chimeric strain), yet increased their intracellular infectivity. This latter effect was unrelated to changes in the hepatocyte secretory pathway, as evidenced using a functional RUSH assay. These results indicate that LARP1 binds to HCV, an event associated with retention of intracellular infectivity.