Proximity labeling of host factor ANXA3 in HCV infection reveals a novel LARP1 function in viral entry.

Hepatitis C virus (HCV) infection is tightly connected to the lipid metabolism with lipid droplets (LDs) serving as assembly sites for progeny virions. A previous LD proteome analysis identified annexin A3 (ANXA3) as an important HCV host factor that is enriched at LDs in infected cells and required for HCV morphogenesis. To further characterize ANXA3 function in HCV, we performed proximity labeling using ANXA3-BioID2 as bait in HCV-infected cells. Two of the top proteins identified proximal to ANXA3 during HCV infection were the La-related protein 1 (LARP1) and the ADP ribosylation factor-like protein 8B (ARL8B), both of which have been previously described to act in HCV particle production. In follow-up experiments, ARL8B functioned as a pro-viral HCV host factor without localizing to LDs and thus likely independent of ANXA3. In contrast, LARP1 interacts with HCV core protein in an RNA-dependent manner and is translocated to LDs by core protein. Knockdown of LARP1 decreased HCV spreading without altering HCV RNA replication or viral titers. Unexpectedly, entry of HCV particles and E1/E2-pseudotyped lentiviral particles was reduced by LARP1 depletion, whereas particle production was not altered. Using a recombinant vesicular stomatitis virus (VSV)ΔG entry assay, we showed that LARP1 depletion also decreased entry of VSV with VSV, MERS, and CHIKV glycoproteins. Therefore, our data expand the role of LARP1 as an HCV host factor that is most prominently involved in the early steps of infection, likely contributing to endocytosis of viral particles through the pleiotropic effect LARP1 has on the cellular translatome.

Guest Encapsulation Alters the Thermodynamic Landscape of a Coordination Host.

The architecture of self-assembled host molecules can profoundly affect the properties of the encapsulated guests. For example, a rigid cage with small windows can efficiently protect its contents from the environment; in contrast, tube-shaped, flexible hosts with large openings and an easily accessible cavity are ideally suited for catalysis. Here, we report a "Janus" nature of a Pd6L4 coordination host previously reported to exist exclusively as a tube isomer (T). We show that upon encapsulating various tetrahedrally shaped guests, T can reconfigure into a cage-shaped host (C) in quantitative yield. Extracting the guest affords empty C, which is metastable and spontaneously relaxes to T, and the T⇄C interconversion can be repeated for multiple cycles. Reversible toggling between two vastly different isomers paves the way toward controlling functional properties of coordination hosts "on demand".

Outcomes of patients discharged home with a chest tube after lung resection: a multicentre cohort study.

BACKGROUND: Prolonged air leaks are increasingly treated in the outpatient setting, with patients discharged with chest tubes in place. We evaluated the incidence and risk factors associated with readmission, empyema development and further interventions in this patient population. METHODS: We undertook a retrospective cohort analysis of all patients from 4 tertiary academic centres (January 2014 to December 2017) who were discharged home with a chest tube after lung resection for a postoperative air leak lasting more than 5 days. We analyzed demographics, patient factors, surgical details, hospital readmission, reintervention, antibiotics at discharge, empyema and death. RESULTS: Overall, 253 of 2794 patients were analyzed (9.0% of all resections), including 30 of 759 from centre 1 (4.0%), 67 of 857 from centre 2 (7.8%), 9 of 247 from centre 3 (3.6%) and 147 of 931 from centre 4 (15.8%) (p < 0.001). Our cohort consisted of 56.5% men, and had a median age of 69 (range 19-88) years. Despite similar initial lengths of stay (p = 0.588), 49 patients (19.4%) were readmitted (21%, 0%, 23% and 11% from centres 1 to 4, respectively, p = 0.029), with 18 (36.7%) developing empyema, 11 (22.4%) requiring surgery and 3 (6.1%) dying. Only chest tube duration was a significant predictor of readmission (p < 0.001) and empyema development (p = 0.003), with a nearly threefold increased odds of developing empyema when the chest tube remained in situ for more than 20 days. CONCLUSION: Discharge with chest tube after lung resection is associated with serious adverse events. Given the high risk of empyema development, removal of chest tubes should be considered, when appropriate, within 20 days of surgery. Our data suggest a potential need for proactive postdischarge outpatient management programs to diminish risk of morbidity and death.

Can a mobile app technology reduce emergency department visits and readmissions after lung resection? A prospective cohort study.

BACKGROUND: Emergency department (ED) visits and readmissions after thoracic surgery are a major health care problem. We hypothesized that the addition of a novel post-discharge mobile app specific to thoracic surgery to an existing home care program would reduce ED visits and readmissions compared to a home care program alone. METHODS: We conducted a prospective cohort study of patients undergoing major lung resection for malignant disease between November 2016 and May 2018. Patients received either home care alone (control group) or home care plus a patient-input mobile app (intervention group). Primary outcomes were 30-day readmission and ED visit rates. Secondary outcomes included reasons for ED visits and readmissions, perioperative complications, 30-day mortality, anxiety (assessed with the Generalized Anxiety Disorder-7 Scale [GAD-7]) and app-related adverse events. We compared outcomes between the 2 groups, analyzing the data on an intention-to-treat basis. RESULTS: Despite the greater number of open surgery and anatomic resections in the intervention cohort, patients in that group were less likely than those in the control group to visit the ED within 30 days of discharge (24.0% v. 38.8%, p = 0.02). Thirty-day readmission rates were similar between the intervention and control groups (10.1% v. 12.2%, p = 0.6). In a subset of patients, there was no difference between the 2 groups in the proportion of patients with a GAD-7 score of 0 (control group 79.8%, intervention group 79.5%, p = NS), which indicated a similar absence of postdischarge anxiety and depression symptoms in the 2 cohorts. CONCLUSION: The addition of a mobile app to a home care program after thoracic surgery was associated with a reduced frequency of ED visits, in spite of the higher proportions of thoracotomies and anatomic resections in the app cohort. More studies are needed to evaluate the full effect of this new, emerging technology.

Endohedrally Functionalized Heteroleptic Coordination Cages for Phosphate Ester Binding.

Metallosupramolecular hosts of nanoscopic dimensions, which are able to serve as selective receptors and catalysts, are usually composed of only one type of organic ligand, restricting diversity in terms of cavity shape and functional group decoration. We report a series of heteroleptic [Pd2 A2 B2 ] coordination cages that self-assemble from a library of shape complementary bis-monodentate ligands in a non-statistical fashion. Ligands A feature an inward pointing NH function, able to engage in hydrogen bonding and amenable to being functionalized with amide and alkyl substituents. Ligands B comprise tricyclic aromatic backbones of different shape and electronic situation. The obtained heteroleptic coordination cages were investigated for their ability to bind phosphate diesters as guests. All-atom molecular dynamics (MD) simulations in explicit solvent were conducted to understand the mechanistic relationships behind the experimentally determined guest affinities.

MiR-100 overexpression attenuates high fat diet induced weight gain, liver steatosis, hypertriglyceridemia and development of metabolic syndrome in mice.

BACKGROUND: Diet-induced obesity can result in the development of a diverse spectrum of cardiovascular and metabolic diseases, including type 2 diabetes, dyslipidemia, non-alcoholic liver steatosis and atherosclerotic disease. MicroRNAs have been described to be important regulators of metabolism and disease development. METHODS: In the current study, we investigated the effects of ubiquitous miR-100 overexpression on weight gain and the metabolic phenotype in a newly generated transgenic mouse strain under normal chow and high fat diet and used microarray expression analysis to identify new potential target genes of miR-100. RESULTS: While transgenic overexpression of miR-100 did not significantly affect weight and metabolism under a normal diet, miR-100 overexpressing mice showed a reduced weight gain under a high fat diet compared to wildtype mice, despite an equal calorie intake. This was accompanied by less visceral and subcutaneous fat development and lover serum LDL cholesterol. In addition, transgenic miR-100 mice were more glucose tolerant and insulin sensitive and demonstrated increased energy expenditure under high fat diet feeding. A comprehensive gene expression profiling revealed the differential expression of several genes involved in lipid storage- and metabolism, among them CD36 and Cyp4A14. Our data showed a direct regulation of CD36 by miR-100, leading to a reduced fatty acid uptake in primary hepatocytes overexpressing miR-100 and the downregulation of several downstream mediators of lipid metabolism such as ACC1, FABP4, FAS and PPARγ in the liver. CONCLUSIONS: Our findings demonstrate a protective role of miR-100 in high fat diet induced metabolic syndrome and liver steatosis, partially mediated by the direct repression of CD36 and attenuation of hepatic lipid storage, implicating miR-100 as a possible therapeutic target in liver steatosis.

The Edmonton Obesity Staging System Predicts Postoperative Complications After Abdominoplasty.

BACKGROUND: This study investigates the relationship between Edmonton Obesity Staging System (EOSS) and the occurrence of postoperative complications after abdominoplasty in massive weight loss patients. METHODS: A single-institution retrospective review of patients undergoing abdominoplasty between 2009 and 2019 after massive weight loss. Demographic data, laboratory findings, known risk factors for postoperative complications, as well as data on major and minor complications were extracted from the patient charts. Logistic regression models were used to investigate the relationship between the variables. RESULTS: Four hundred and five patients were included in the study. The prevalence of EOSS stages was: 0 (no comorbidities, N = 151, 37%), 1 (mild conditions, N = 40, 10%), 2 (moderate conditions, N = 149, 36%) and 3 (severe conditions, N = 70, 17%). Regression analysis showed that, controlling for body mass index (BMI), BMI Δ (maximal BMI - BMI at presentation), bariatric surgery, volume of resected tissue, and duration of surgery, EOSS stage significantly associated with the occurrence of postoperative complications. Compared with EOSS stage 0, EOSS stages 2 and 3 patients were associated with significantly more minor and major complications, respectively. The volume of resected tissue, BMI Δ, and age were associated with the occurrence of major complications. A regression model of comorbidities comprising the EOSS revealed a significant association of variables diabetes mellitus and hypertension with the occurrence of postoperative complications. CONCLUSIONS: Edmonton Obesity Staging System is a robust predictor of postoperative complications in abdominoplasty.

MicroRNA-100 Suppresses Chronic Vascular Inflammation by Stimulation of Endothelial Autophagy.

RATIONALE: The interaction of circulating cells within the vascular wall is a critical event in chronic inflammatory processes, such as atherosclerosis, but the control of the vascular inflammatory state is still largely unclear. OBJECTIVE: This study was undertaken to characterize the function of the endothelial-enriched microRNA miR-100 during vascular inflammation and atherogenesis. METHODS AND RESULTS: Based on a transcriptome analysis of endothelial cells after miR-100 overexpression, we identified miR-100 as a potent suppressor of endothelial adhesion molecule expression, resulting in attenuated leukocyte-endothelial interaction in vitro and in vivo as shown by flow cytometry and intravital imaging. Mechanistically, miR-100 directly repressed several components of mammalian target of rapamycin complex 1-signaling, including mammalian target of rapamycin and raptor, which resulted in a stimulation of endothelial autophagy and attenuated nuclear factor κB signaling in vitro and in vivo. In a low-density lipoprotein receptor-deficient atherosclerotic mouse model, pharmacological inhibition of miR-100 resulted in enhanced plaque lesion formation and a higher macrophage content of the plaque, whereas a systemic miR-100 replacement therapy had protective effects and attenuated atherogenesis, resulting in a decrease of plaque area by 45%. Finally, analysis of miR-100 expression in >70 samples obtained during carotid endarterectomy revealed that local miR-100 expression was inversely correlated with inflammatory cell content in patients. CONCLUSIONS: In summary, we describe an anti-inflammatory function of miR-100 in the vascular response to injury and inflammation and identify an important novel modulator of mammalian target of rapamycin signaling and autophagy in the vascular system. Our findings of miR-100 as a potential protective anti-athero-miR suggest that the therapeutic replacement of this microRNA could be a potential strategy for the treatment of chronic inflammatory diseases, such as atherosclerosis, in the future.

A New Mechanically-Interlocked [Pd2 L4 ] Cage Motif by Dimerization of two Peptide-based Lemniscates.

Most metallo-supramolecular assemblies of low nuclearity adopt simple topologies, with bridging ligands spanning neighboring metal centers in a direct fashion. Here we contribute a new structural motif to the family of host compounds with low metal count (two) that consists of a pair of doubly-interlocked, Figure-eight-shaped subunits, also termed "lemniscates". Each metal is chelated by two chiral bidentate ligands, composed of a peptidic macrocycle that resembles a natural product with two pyridyl-terminated arms. DFT calculation results suggest that dimerization of the mononuclear halves is driven by a combination of 1) Coulomb interaction with a central anion, 2) π-stacking between intertwined ligand arms and 3) dispersive interactions between the structure's compact inner core bedded into an outer shell composed of the cavitand-type macrocycles. The resulting cage-like architecture was characterized by NMR, MS and X-ray structure analyses. This new mechanically bonded system highlights the scope of structural variety accessible in metal-mediated self-assemblies composed of only a few constituents.

Orf virus infection of human keratinocytes and dermal fibroblasts: Limited virus detection and interference with intercellular adhesion molecule-1 up-regulation.

Orf virus (Parapoxvirus ovis, ORFV) is a dermatotropic virus causing pustular dermatitis in small ruminants and humans. We analysed isolated human primary keratinocytes (KC) and dermal fibroblasts (FB) for cell death and virus replication by infection with a patient-derived ORFV isolate. ORFV infection was associated with rapid induction of cell death in KC allowing for considerable virus removal. Upon infection with ORFV, KC and FB harboured intracytoplasmic ORFV and showed viral protein presence; however, missing virus spread indicated an abortive infection. Upon ORFV exposure, KC but not FB secreted the pro-inflammatory cytokine interleukin (IL)-6. ORFV infection enhanced the frequency of KC expressing intercellular adhesion molecule (ICAM)-1 which was independent of IL-6. Interestingly, ORFV inhibited ICAM-1 up-regulation on infected but not on non-infected KC. Even interferon-γ, a potent inducer of ICAM-1, up-regulated ICAM-1 only on non-infected KC. Transfer of ORFV-free supernatant from infected to non-infected KC induced ICAM-1 on non-infected KC pointing to the involvement of soluble mediator(s). Similarly as in KC, in FB interference with ICAM-1 up-regulation by ORFV infection was also observed. In conclusion, we shed light on epidermal and dermal defense mechanisms to ORFV infection and point to a novel ICAM-1-related immune evasion mechanism of ORFV in human skin.

Care Delivery Patterns, Processes, and Outcomes for Primary Ovarian Cancer Surgery: A Population-Based Review Using a National Administrative Database.

OBJECTIVES: In this pan-Canadian study, we sought to elucidate the current state of surgical care for primary ovarian cancers and factors influencing selected short-term outcomes; these were in-hospital mortality (IHM), major complications (MCs), failure-to-rescue (FTR), and hospital length of stay (LOS). METHODS: We created a population cohort using inpatient admission records from the Canadian Institute of Health Information data set (2004-2012). Multilevel logistic regression and flexible parametric survival analyses, adjusted for hospital clustering effect, were conducted to determine the effect of patient-specific factors (i.e., age, comorbidities, and admission category); procedural complexity; and the surgical volume and specialty of each care provider on the outcomes of interest. RESULTS: A total of 16 089 women underwent surgeries for primary ovarian cancer across Canada. The crude rates of IHM, MC, and FTR were 0.89%, 5.7%, and 9.09%, respectively, with a median LOS of four days (interquartile range 3 to 6). The majority of surgical procedures were performed by surgeons and hospitals with annual surgical volumes of less than five such procedures. Hospitals with higher surgical volumes were associated with lower risk of IHM (OR 0.95, 95% CI 0.91 to 0.99) and FTR (OR 0.95, 95% CI 0.91 to 0.99) and a higher chance of earlier discharge (hazard ratio [HR] 1.03, 95% CI 1.00 to 1.06). Surgeons with higher surgical volumes were associated with lower odds of early discharge (HR 0.90, 95% CI 0.87 to 0.94) and a higher risk of MC (OR 1.12, 95% CI 1.02 to 1.23). Compared with gynaecologic oncologists, general surgeons had a significantly higher risk of IHM (OR 3.50, 95% CI 1.82 to 6.74) and MC (OR 2.13, 95% CI 1.36 to 3.33) and lower odds of early discharge (HR 0.43, 95% CI 0.40 to 0.47). CONCLUSION: Despite limitations in the administrative data set, valuable information was available for this pan-Canadian analysis. Our findings support centralization of surgical procedures for women with ovarian cancer in tertiary care centres with higher surgical volumes that are staffed by in-house multidisciplinary care teams and specialist surgeons.

Highly Enantioselective Catalytic Vinylogous Propargylation of Coumarins Yields a Class of Autophagy Inhibitors.

A highly enantioselective copper-catalyzed vinylogous propargylic substitution has been developed. Aromatic and aliphatic propargylic esters react smoothly with substituted coumarins under mild reaction conditions to give the desired products with excellent yields and enantioselectivities. Subsequent single-step transformations enable the synthesis of a wide range of multifunctional and diverse compounds, and allow the efficient combination of different natural product fragments. Investigation of the obtained compound collection in cell-based assays monitoring changes in phenotype led to the discovery of a novel class of autophagy inhibitors.

Developmental Programming of Branching Morphogenesis in the Kidney.

The kidney developmental program encodes the intricate branching and organization of approximately 1 million functional units (nephrons). Branching regulation is poorly understood, as is the source of a 10-fold variation in nephron number. Notably, low nephron count increases the risk for developing hypertension and renal failure. To better understand the source of this variation, we analyzed the complete gestational trajectory of mouse kidney development. We constructed a computerized architectural map of the branching process throughout fetal life and found that organogenesis is composed of two distinct developmental phases, each with stage-specific rate and morphologic parameters. The early phase is characterized by a rapid acceleration in branching rate and by branching divisions that repeat with relatively reproducible morphology. The latter phase, however, is notable for a significantly decreased yet constant branching rate and the presence of nonstereotyped branching events that generate progressive variability in tree morphology until birth. Our map identifies and quantitates the contribution of four developmental mechanisms that guide organogenesis: growth, patterning, branching rate, and nephron induction. When applied to organs that developed under conditions of malnutrition or in the setting of growth factor mutation, our normative map provided an essential link between kidney architecture and the fundamental morphogenetic mechanisms that guide development. This morphogenetic map is expected to find widespread applications and help identify modifiable targets to prevent developmental programming of common diseases.

Assessing Nursing Care Needs of Children With Complex Medical Conditions: The Nursing-Kids Intensity of Care Survey (N-KICS).

UNLABELLED: Recent medical advances have resulted in increased survival of children with complex medical conditions (CMC), but there are no validated methods to measure their care needs. OBJECTIVES/METHODS: To design and test the Nursing-Kids Intensity of Care Survey (N-KICS) tool and describe intensity of nursing care for children with CMC. RESULTS: The psychometric evaluation confirmed an acceptable standard for reliability and validity and feasibility. Intensity scores were highest for nursing care related to infection control, medication administration, nutrition, diaper changes, hygiene, neurological and respiratory support, and standing program. CONCLUSIONS: Development of a psychometrically sound measure of nursing intensity will help evaluate and plan nursing care for children with CMC.

Discovery of New Classes of Compounds that Reactivate Acetylcholinesterase Inhibited by Organophosphates.

Acetylcholinesterase (AChE) that has been covalently inhibited by organophosphate compounds (OPCs), such as nerve agents and pesticides, has traditionally been reactivated by using nucleophilic oximes. There is, however, a clearly recognized need for new classes of compounds with the ability to reactivate inhibited AChE with improved in vivo efficacy. Here we describe our discovery of new functional groups--Mannich phenols and general bases--that are capable of reactivating OPC--inhibited AChE more efficiently than standard oximes and we describe the cooperative mechanism by which these functionalities are delivered to the active site. These discoveries, supported by preliminary in vivo results and crystallographic data, significantly broaden the available approaches for reactivation of AChE.

[Robotic-Assisted DIEP Flap Harvest for Autologous Breast Reconstruction: Case Report, Technical Aspects and Identification of Suitable Patients]. / Die robotisch-assistierte Hebung der DIEP-Lappenplastik zur Brustrekonstruktion: Fallbericht, technische Aspekte und Identifikation geeigneter Patientinnen.

BACKGROUND: Robotic-assisted harvest of the deep inferior epigastric perforator (DIEP) flap is an innovative modification of the traditional open preparation for autologous breast reconstruction. It is assumed that donor-site morbidity (herniae, bulging) is reduced by minimising the fascial incision length in robotic-assisted DIEP flap harvest. MATERIAL & METHODS: This is the first report of a robotic-assisted DIEP harvest in Germany, which was performed in April 2023 at the University Hospital of Freiburg in an interdisciplinary approach of the Departments of Plastic Surgery, Urology and Gynaecology. To determine the value of this novel technique, we assessed the demand by retrospectively performing an analysis of potential patients and conducted a cost analysis based on the breast reconstructions with DIEP flap harvest performed between April 2021 and May 2023 at the Department of Plastic Surgery at Freiburg University Hospital. To this end, we carried out a retrospective analysis of preoperative CT angiographies to determine the proportion of patients suitable for a robotic-assisted procedure in a post-hoc analysis. Furthermore, we describe the basic robotic-assisted techniques and discuss the TEP and TAPP laparoscopic approaches. RESULTS: In line with the previously published literature, a short intramuscular course (≤25 mm) and a perforator diameter of≥1.5 mm and≥2.7 mm (subgroup) were defined as a crucial condition for the robotic-assisted procedure. We analysed 65 DIEP flaps harvested in 51 patients, of which 26 DIEP flaps in 22 patients met both criteria, i. e.≤25 mm intramuscular course and≥1.5 mm diameter of the perforator, while 10 DIEP flaps in 10 patients additionally met the criteria of the subgroup (≥2.7 mm diameter). Based on the intramuscular course of the perforators in the CT angiographies of those 26 DIEP flaps, a potential reduction of the fascial incision of 96.8±25.21 mm (mean±standard deviation) compared with the conventional surgical approach was calculated. The additional material costs in our case were EUR 986.01. However, ischaemia time was 33,5 minutes longer than the median of the comparative cohort. CONCLUSION: The robotic-assisted procedure has already proven to be a feasible alternative in a suitable patient population. However, further studies are needed to confirm that robotic-assisted DIEP flap harvest actually reduces harvest site morbidity and thereby justifies the additional costs and complexity.

C-reactive protein orchestrates acute allograft rejection in vascularized composite allotransplantation via subset-selective monocyte activation.

INTRODUCTION: Despite recent substantial progress in vascularized composite allotransplantation (VCA), such as face transplantations, short- and long-term allograft survival is severely limited by allograft rejection. The acute-phase response, directly after allogeneic transplantation, represents an immune-inflammatory reaction to ischemia/reperfusion and acts as an early initiator of graft rejection. Acute-phase reactants mediate this immune response via crosstalk with the mononuclear phagocyte system. OBJECTIVE: C-reactive protein (CRP), a well-known marker of inflammation, has pro-inflammatory properties and aggravates ischemia/reperfusion injury. Thus, we investigated how CRP impacts acute allograft rejection. METHODS: Based on clinical observations in facial VCAs, we applied a complex hindlimb transplantation model in rats to investigate whether CRP directly affects transplant rejection. We further analyzed subset-specific infiltration and tissue distribution of recipient-derived monocytes in the early phase of acute rejection and assessed their differential regulation by CRP using intravital imaging. RESULTS: We demonstrate that CRP accelerates allograft rejection and reduces allograft survival via selectively activating non-classical monocytes. The therapeutic stabilization of CRP abrogates this activating effect on monocytes, consequently attenuating acute allograft rejection. Intravital imaging of graft-infiltrating, recipient-derived monocytes during the early phase of acute rejection confirmed their differential regulation by CRP and their crucial role in driving the early stage of graft rejection. CONCLUSION: Differential activation of recipient-derived monocytes by CRP aggravates innate immune response and accelerates clinical allograft rejection Thus, therapeutic targeting of CRP represents a novel promising strategy for preventing acute allograft rejection and potentially reducing chronic allograft rejection.

Phosphatidylserine-exposing extracellular vesicles in body fluids are an innate defence against apoptotic mimicry viral pathogens.

Some viruses are rarely transmitted orally or sexually despite their presence in saliva, breast milk, or semen. We previously identified that extracellular vesicles (EVs) in semen and saliva inhibit Zika virus infection. However, the antiviral spectrum and underlying mechanism remained unclear. Here we applied lipidomics and flow cytometry to show that these EVs expose phosphatidylserine (PS). By blocking PS receptors, targeted by Zika virus in the process of apoptotic mimicry, they interfere with viral attachment and entry. Consequently, physiological concentrations of EVs applied in vitro efficiently inhibited infection by apoptotic mimicry dengue, West Nile, Chikungunya, Ebola and vesicular stomatitis viruses, but not severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus 1, hepatitis C virus and herpesviruses that use other entry receptors. Our results identify the role of PS-rich EVs in body fluids in innate defence against infection via viral apoptotic mimicries, explaining why these viruses are primarily transmitted via PS-EV-deficient blood or blood-ingesting arthropods rather than direct human-to-human contact.