Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of enterovirus 71 in crossing an in vitro model of human blood brain barrier

Human cerebral microvascular endothelial cells (hCMEC/D3 cell line) form a steady polarized barrier when cultured in vitro on a permeable membrane. Their susceptibility to enterovirus (EV) strains was analysed to investigate how these viruses may cross the blood-brain barrier. A sample of 88 virus strains was selected on phylogenetic features among 44 epidemiologically relevant types of the four EV species A-D. The EV-A71 genome was replicated at substantial rates while the infectious virus was released at extremely low but sustained rates at both barrier sides for at least 4 days. EV-A71 antigens were detected in a limited number of cells. The properties of the endothelial barrier (structure and permeability) remained intact throughout infection. The chronic EV-A71 infection was in sharp contrast with the productive infection of cytolytic EVs (e.g. echoviruses 6 and 30). The hCMEC/D3 barriers infected with the latter EVs exhibited elevated proportions of apoptotic and necrotic cells, which resulted in major injuries to the endothelial barriers with dramatic increase of paracellular permeability and virus crossing to the abluminal side. The following intracellular rearrangements were also seen: early destruction of the actin cytoskeleton, remodelling of intracellular membranes, and reorganization of the mitochondrion network in a small cluster near the perinuclear space

Echovirus 30, Jiangsu Province, China

Global increase in outbreaks due to E30 indicates that detailed understanding of the transmission and evolution of enteroviruses is urgently needed

Evolutionary history of hepatitis C virus genotype 5a in France, a multicenter ANRS study

The epidemic history of HCV genotype 5a is poorly documented in France, where its prevalence is very low, except in a small central area, where it accounts for 14.2% of chronic hepatitis C cases. A Bayesian coalescent phylogenetic investigation based on the E1 envelope gene and a non-structural genomic segment (NS3/4) was carried out to trace the origin of this epidemic using a large sample of genotype 5a isolates collected throughout France. The dates of documented transmissions by blood transfusion were used to calibrate five nodes in the phylogeny. The results of the E1 gene analysis showed that the best-fitting population dynamic model was the expansion growth model under a relaxed molecular clock. The rate of nucleotide substitutions and time to the most recent common ancestors (tMRCA) of genotype 5a isolates were estimated. The divergence of all the French HCV genotype 5a strains included in this study was dated to 1939 [95% HPD: 1921–1956], and the tMRCA of isolates from central France was dated to 1954 [1942–1967], which is in agreement with epidemiological data. NS3/4 analysis provided similar estimates with strongly overlapping HPD values. Phylodynamic analyses give a plausible reconstruction of the evolutionary history of HCV genotype 5a in France, suggesting the concomitant roles of transfusion, iatrogenic route and intra-familial transmission in viral diffusion

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old

Acute flaccid myelitis and enteroviruses: an ongoing story

International audienc

Symptomatologie et évolution de la maladie « pieds-mains-bouche »

International audienceHand, foot and mouth disease (HFMD) and herpangina (HA) are common childhood diseases mostly associated with human enteroviruses (EV). Although usually benign illnesses, neurological complications may be observed during large epidemics when enterovirus A71 (EV-A71) is involved, as observed in the Asia Pacific Region and in China since the late 1990s. The occurrence of these complications warrants reinforcing the surveillance of the emergence of EV-A71 infections in France and Europe. Monitoring EV infections associated with HFMD can be considered as an effective tool to detect an upsurge of EV-A71 infections in a timely manner. In 2014, a national sentinel surveillance system for HFMD/HA was set up in France through a network of volunteer pediatricians and coordinated by the National Reference Center for Enteroviruses and Parechoviruses. Although classical manifestations of HFMD/HA can be easily recognized, there are Archives de Pédiatrie 24 (Elsevier Masson SAS. Tous droits réservés. several atypical presentations of the disease that can be confused with other skin conditions. Delayed cutaneous manifestations, such as onychomadesis and acral desquamation, may also occur and should prompt consideration of HFMD in the preceding weeks. Severe complications following HFMD include neurological manifestations (mainly rhombencephalitis) or less frequently cardiopulmonary failure and can sometimes be fatal. In China, the case severity rate has been estimated at 1%, with a case fatality rate at 0.03%. EV-A71 was involved in more than 90% of the fatal cases. Diagnosis of EV infections associated with severe neurological manifestations is based on the molecular detection of the EV genome in vesicles, cerebrospinal fluid (CSF), throat and stool given that EV-A71 is rarely recovered from the CSF. Positive EV genome detection should be followed by EV genotyping to identify the type of the EV. In temperate-climate countries, outbreaks of HFMD occur mostly but not exclusively during summer and autumn months. Adults may also present with HFMD. In 2016, an upsurge of severe neurological manifestations was reported in France; EV-A71 accounted for 50% of the cases. No specific treatment is available, but two inactivated EV-A71 vaccines are currently available in China.La maladie pieds-mains-bouche (PMB), le plus souvent bénigne, est associée à des infections à entérovirus, surtout le coxsackievirus A16 et l'entérovirus A71 (EV-A71). Lors des grandes épidémies en Asie du Sud-Est et en Chine survenues depuis la fin 1990, les complications neurologiques à type d'encéphalite ou de paralysie flasque aiguë impliquaient toutes l'EV-A71. La maladie PMB apparaît comme un excellent marqueur épidémiologique de l'EV-A71. Elle est surveillée en France depuis 2014 grâce à un réseau de pédiatres volontaires et sous l'égide du Centre national de référence (CNR). À côté des formes typiques, de nombreuses formes atypiques extensives sont trompeuses, de même que les manifestations tardives telles qu'une desquamation de la paume des mains et de la plante des pieds ou une onychomadèse. Les complications neurologiques, et plus rarement cardiopulmonaires, survenant au décours de la maladie sont parfois mortelles. En Chine, leur taux de survenue a été estimé à environ 1 % avec un taux de mortalité de 0,03 %. L'EV-71 est présent dans plus de 90 % des décès. Le diagnostic virologique dans les formes sévères fait appel à la recherche du virus par amplification génique inverse et à son génotypage, dans les lésions cutanéo-muqueuses, le liquide céphalorachidien (LCR), la gorge et les selles car l'EV-A71 est rarement retrouvé dans le LCR. Dans les pays tempérés, la maladie PMB évolue sur un mode épidémique biphasique et sur un mode endémique, touchant aussi les adultes. En 2016, une recrudescence d'atteintes neurologiques sévères, dont la moitié attribuée à l'EV-A71, est survenue en France. Il n'y a pas de traitement spécifique, mais deux vaccins inactivés sont disponibles en Chine