The neuraminidase activity of influenza A virus determines the strain-specific sensitivity to neutralization by respiratory mucus.

IMPORTANCE: The respiratory tract of humans is constantly exposed to potentially harmful agents, such as small particles or pathogens, and thus requires protective measures. Respiratory mucus that lines the airway epithelia plays a major role in the prevention of viral infections by limiting the mobility of viruses, allowing subsequent mucociliary clearance. Understanding the interplay between respiratory mucus and viruses can help elucidate host and virus characteristics that enable the initiation of infection. Here, we tested a panel of primary influenza A viruses of avian or human origin for their sensitivity to mucus derived from primary human airway cultures and found that differences between virus strains can be mapped to viral neuraminidase activity. We also show that binding of influenza A viruses to decoy receptors on highly glycosylated mucus components constitutes the major inhibitory function of mucus against influenza A viruses.

Broad and Dynamic Diversification of Infectious Hepatitis C Virus in a Cell Culture Environment.

Previous studies documented that long-term hepatitis C virus (HCV) replication in human hepatoma Huh-7.5 cells resulted in viral fitness gain, expansion of the mutant spectrum, and several phenotypic alterations. In the present work, we show that mutational waves (changes in frequency of individual mutations) occurred continuously and became more prominent as the virus gained fitness. They were accompanied by an increasing proportion of heterogeneous genomic sites that affected 1 position in the initial HCV population and 19 and 69 positions at passages 100 and 200, respectively. Analysis of biological clones of HCV showed that these dynamic events affected infectious genomes, since part of the fluctuating mutations became incorporated into viable genomes. While 17 mutations were scored in 3 biological clones isolated from the initial population, the number reached 72 in 3 biological clones from the population at passage 200. Biological clones differed in their responses to antiviral inhibitors, indicating a phenotypic impact of viral dynamics. Thus, HCV adaptation to a specific constant environment (cell culture without external influences) broadens the mutant repertoire and does not focus the population toward a limited number of dominant genomes. A retrospective examination of mutant spectra of foot-and-mouth disease virus passaged in cell cultures suggests a parallel behavior here described for HCV. We propose that virus diversification in a constant environment has its basis in the availability of multiple alternative mutational pathways for fitness gain. This mechanism of broad diversification should also apply to other replicative systems characterized by high mutation rates and large population sizes.IMPORTANCE The study shows that extensive replication of an RNA virus in a constant biological environment does not limit exploration of sequence space and adaptive options. There was no convergence toward a restricted set of adapted genomes. Mutational waves and mutant spectrum broadening affected infectious genomes. Therefore, profound modifications of mutant spectrum composition and consensus sequence diversification are not exclusively dependent on environmental alterations or the intervention of population bottlenecks.

Diseño de un observatorio de Equidad en Calidad de Vida y Salud para Bogotá / Design of an observatory of equity as life and health for Bogota

El artículo recoge los resultados del trabajo realizado por el Grupo de Protección Social del Centro de Investigaciones para el Desarrollo (CID) de la Facultad de Ciencias Económicas de la Universidad Nacional de Colombia, en el marco del Convenio interadministrativo con la Secretaría Distrital de Salud (SDS), para la elaboración de una propuesta de diseño de un observatorio de equidad en calidad de vida y salud para Bogotá. Con tal propósito se realizó una revisión minuciosa del debate internacional y nacional sobre el tema de la equidad en salud, como punto de partida para la formulación de un enfoque teórico para el observatorio. Adicionalmente se revisó la experiencia de los observatorios de equidad en salud de las ciudades de Londres, Bruselas y Montreal, como referentes internacionales para el diseño. Con base en lo anterior, se elaboró una propuesta de diseño del observatorio que incluye el enfoque teórico adoptado, los objetivos, los procesos centrales, los métodos y la estructura básica de operación. Tratándose de un diseño, la operación del observatorio será el resultado de nuevas decisiones institucionales, si se considera que la propuesta presentada aquí tiene lugar, importancia y viabilidad para el futuro de la ciudad.

The article summarizes the results of the work done by the Social Protection Group of the Development Investigation Center (CID) of the Faculty of Economic Sciences of the National University of Colombia, according to the interadministrative agreement with the District Secretary of Health (SDS), for the elaboration of a design proposal for an observatory for equity in quality of life and health in Bogotá. With this in mind, they undertook a minute review of national and international debates on the subject of equity in health, as a point of departure for the formulation of a theoretical basis for the observatory. Additionally they reviewed the experiences of such equity in health observatories in cities such as London, Brussels, and Montreal, as international referents for the design. Based on the above, they created a design proposal for the observatory that includes the adopted theoretical focus, the objectives, the central processes, the methods and the basic structure of the operation. Speaking of this design, the operation of the observatory will come about through new institutional decisions, if the present proposal is considered to be important and viable for the future of the city.