EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease.

Microplastic accumulation in sewer sediments and its potential entering the environment via combined sewer overflows: a study case in Paris.

During wet weather events, combined sewer overflows (CSOs) transfer large amount of particulate matter and associated pollutants into surrounding water bodies, thereby deteriorating the recipients' ecological health. Resuspension of sewer sediments during these events contributes significantly to pollution level of these discharges. However, how much this in-sewer process contributes to CSOs' quality regarding microplastic (MP) pollution is little known. Therefore, an investigation on sewer deposits inside the Parisian combined sewer network was carried out. The study found high MP concentrations stored in this matrix, ranging from 5 × 103 to 178 × 103 particle/kg dry weight. Polymer composition is similar to what found in raw wastewater, containing a high proportion of polyethylene and polypropylene. Thus, the results indicated the persistence of MPs in sewer network during transport during dry weather periods to treatment facilities. Once resuspension of sewer deposits happens, MPs can be released into water flow and get discharged along with CSOs. This highlights another potential pathway of MPs into freshwater environment.

Microplastics in two German wastewater treatment plants: Year-long effluent analysis with FTIR and Py-GC/MS.

Microplastics (MP) have been recorded in various environments around the globe. For a better understanding of distribution patterns and for providing a basis for risk assessments, detailed data on MP concentrations and polymer compositions are required. This study investigated the effluents of two German wastewater treatment plants (WWTP) monthly over one year, in order to better understand their temporal input of MP into the receiving river systems. MP item data down to 11 µm were obtained by means of Fourier Transform Infrared (FTIR) spectroscopy under the application of an improved polymer database. Complementary mass data were obtained by pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) (for one WWTP). Both FTIR and Py-GC/MS analysis revealed a homogeneous polymer composition over the year, with a general dominance of polyolefins. Elevated MP item and mass concentrations (maximum: 3 × 104 items m-3 and 3.8 × 103 µg m-3) were observed during winter months and were accompanied by either heavy rainfall (increased discharge and total organic carbon) or elevated turbidity values. These observations emphasize the need for the assessment of background parameters in future MP monitoring studies. By providing monthly data over one year on MP items and masses in WWTP effluents, this study helps enhancing the understanding of temporal MP dynamics and can act as a valuable reference point for future assessments.

Cross-Sectional Analysis of the Microbiota of Human Gut and Its Direct Environment in a Household Cohort with High Background of Antibiotic Use.

Comprehensive insight into the microbiota of the gut of humans and animals, as well as their living environment, in communities with a high background of antibiotic use and antibiotic resistance genes is scarce. Here, we used 16S rRNA gene sequencing to describe the (dis)similarities in the microbiota of feces from humans (n = 107), domestic animals (n = 36), water (n = 89), and processed food (n = 74) in a cohort with individual history of antibiotic use in northern Vietnam. A significantly lower microbial diversity was observed among individuals who used antibiotics in the past 4 months (n = 44) compared to those who did not (n = 63). Fecal microbiota of humans was more diverse than nonhuman samples and shared a small part of its amplicon sequence variants (ASVs) with feces from animals (7.4% (3.2-9.9)), water (2.2% (1.2-2.8)), and food (3.1% (1.5-3.1)). Sharing of ASVs between humans and companion animals was not associated with the household. However, we did observe a correlation between an Enterobacteriaceae ASV and the presence of extended-spectrum beta-lactamase CTX-M-group-2 encoding genes in feces from humans and animals (p = 1.6 × 10-3 and p = 2.6 × 10-2, respectively), hinting toward an exchange of antimicrobial-resistant strains between reservoirs.

A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques.

As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.

Recent advances of vaccine adjuvants for infectious diseases.

Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases.