Summary Genetic defects in MOGS, the gene encoding mannosyl-oligosaccharide glucosidase (the first enzyme in the processing pathway of N-linked oligosaccharide), cause the rare congenital disorder of glycosylation type IIb (CDG-IIb), also known as MOGS-CDG. MOGS is expressed in the endoplasmic reticulum and is involved in the trimming of N-glycans. We evaluated two siblings with CDG-IIb who presented with multiple neurologic complications and a paradoxical immunologic phenotype characterized by severe hypogammaglobulinemia but limited clinical evidence of an infectious diathesis. A shortened immunoglobulin half-life was determined to be the mechanism underlying the hypogammaglobulinemia. Impaired viral replication and cellular entry may explain a decreased susceptibility to infections.

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Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as "Category A bioterrorism agents", and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development including recombinant adenovirus, parainfluenza virus, Venezuelan equine encephalitis virus, vesicular stomatitis virus (VSV) and virus-like particles. Here we describe the development of a GP Fc fusion protein as a vaccine candidate. We expressed the extracellular domain of the Zaire Ebola virus (ZEBOV) GP fused to the Fc fragment of human IgG1 (ZEBOVGP-Fc) in mammalian cells and showed that GP undergoes the complex furin cleavage and processing observed in the native membrane-bound GP. Mice immunized with ZEBOVGP-Fc developed T-cell immunity against ZEBOV GP and neutralizing antibodies against replication-competent VSV-G deleted recombinant VSV containing ZEBOV GP. The ZEBOVGPFc vaccinated mice were protected against challenge with a lethal dose of ZEBOV. These results show that vaccination with the ZEBOVGP-Fc fusion protein alone without the need of a viral vector or assembly into virus-like particles is sufficient to induce protective immunity against ZEBOV in mice. Our data suggested that Filovirus GP Fc fusion proteins could be developed as a simple, safe, efficacious, and cost effective vaccine against Filovirus infection for human use.

Enteroviruses (EVs) can induce nonspecific respiratory tract infections in children, but their epidemiological, virological, and clinical features remain to be assessed. In the present study, we analyzed 252 EV-related infection cases (median age of subjects, 5.1 years) diagnosed among 11,509 consecutive children visiting emergency departments within a 7-year period in the north of France. EV strains were isolated from nasopharyngeal samples by viral cell culture, identified by seroneutralization assay, and genetically compared by partial amplification and sequencing of the VP1 gene. ؊3 ) occurring more often in infants aged 1 to 12 months (P ‫؍‬ 0.0002), with spring-fall seasonality. Viruses ECHO 11, 6, and 13 were the more frequently identified respiratory strains (24, 13, and 11%, respectively). The VP1 gene phylogenetic analysis showed the concomitant or successive circulation of genetically distinct EV respiratory strains (species A or B) during the same month or annual epidemic period. Our findings indicated that respiratory tract infections accounted for the 30% of EV-induced pediatric pathologies, contributing to LRTIs in 54% of these cases. Moreover, the concomitant or successive circulation of genetically distinct EV strains indicated the possibility of pediatric repeated respiratory infections within the same epidemic season.Enteroviruses (EVs) (Picornaviridae) are among the most common viruses infecting human beings worldwide (13,23,25). Current taxonomy divides nonpolio human EV into four species (human EVs A to D), including a total of 89 serotypes (24, 38). Individual serotypes have different temporal patterns of circulation and can be associated with different clinical manifestations (24, 39). Although the majority of human EV infections remain asymptomatic, these viruses are associated with diverse clinical syndromes, ranging from minor febrile illness to severe and potentially fatal pathologies, including aseptic meningitis, encephalitis, myopericarditis, acute flaccid paralysis, and severe neonatal sepsis-like disease (24). Moreover, EV can induce nonspecific respiratory illnesses in infants or adults, including upper respiratory tract infections but also lower respiratory tract infections (LRTIs), resulting in bronchitis, bronchiolitis (37), and pneumonia (13). Different human EV strains-including EV 68 and 71, coxsackie A9, A21, B2 and B4 viruses, and echovirus 9, 11 and 22-have been isolated from nasopharyngeal samples, tracheal aspirates, bronchoalveolar lavages, or lung tissues by classical cell culture assays and identified as the cause of severe or fatal viral bronchopneumonia (4,6,10,11,29,32,35). At present, our understanding of the epidemiology and clinical profile of EV pediatric respiratory infections is restricted to the prevalence and the epidemiological significance of EV respiratory infections as the cause of bronchiolitis or acute wheezing in cohorts of hospitalized infants (1,22,31,33). In these reports, no serotyping identification or molecular comparative analysis of EV res...

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Our data suggest that HBoV at a high viral load could be an etiologic agent of respiratory tract disease, whereas the exact role of HBoV at a low viral load, as etiological cause or as pathophysiological co-factor of respiratory diseases, remains to be determined.

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