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Characteristics of exhaled particle production in healthy volunteers: possible implications for infectious disease transmission.

ABSTRACT: The size and concentration of exhaled particles may influence respiratory infection transmission risk. We assessed variation in exhaled particle production between individuals, factors associated with high production and stability over time. We measured exhaled particle production during tidal breathing in a sample of 79 healthy volunteers, using optical particle counter technology. Repeat measurements (several months after baseline) were obtained for 37 of the 79 participants. Multilevel linear regression models of log transformed particle production measures were used to assess risk factors for high production. Stability between measurements over time was assessed using Lin's correlation coefficients. Ninety-nine percent of expired particles were <1?m in diameter. Considerable variation in exhaled particle production was observed between individuals and within individuals over time. Distribution of particle production was right skewed. Approximately 90% of individuals produce <150 particles per litre in normal breathing. A few individuals had measurements of over 1000 particles per litre (maximum 1456). Particle production increased with age (p<0.001) and was associated with high tree pollen counts. Particle production levels did not remain stable over time [rho 0.14 (95%CI -0.10, 0.38, p=0.238)]. Sub-micron particles conducive to airborne rather than droplet transmission form the great majority of exhaled particles in tidal breathing. There is a high level of variability between subjects but measurements are not stable over time. Production increases with age and may be influenced by airway inflammation caused by environmental irritants. Further research is needed to determine whether the observed variations in exhaled particle production affect transmission of respiratory infection.

SUBMITTER: Wurie F

PROVIDER: S-EPMC3901511 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Characteristics of exhaled particle production in healthy volunteers: possible implications for infectious disease transmission.

Wurie Fatima F Le Polain de Waroux Olivier O Brande Matthew M Dehaan Wesley W Holdgate Katherine K Mannan Rishi R Milton Donald D Swerdlow Daniel D Hayward Andrew A

F1000Research 20130115

The size and concentration of exhaled particles may influence respiratory infection transmission risk. We assessed variation in exhaled particle production between individuals, factors associated with high production and stability over time. We measured exhaled particle production during tidal breathing in a sample of 79 healthy volunteers, using optical particle counter technology. Repeat measurements (several months after baseline) were obtained for 37 of the 79 participants. Multilevel line ...[more]

PMID: 24555026

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Project description:Ebola virus (EBOV) protein VP24 carries out at least two critical functions. It promotes condensation of viral nucleocapsids, which is crucial for infectious virus production, and it suppresses interferon (IFN) signaling, which requires interaction with the NPI-1 subfamily of importin-α (IMPA) nuclear transport proteins. Interestingly, over-expressed IMPA leads to VP24 nuclear accumulation and a carboxy-terminus nuclear export signal (NES) has been reported, suggesting that VP24 may undergo nuclear trafficking. For the first time, we demonstrate that NPI-1 IMPA overexpression leads to the nuclear accumulation of VP24 during EBOV infection. To assess the functional impact of nuclear trafficking, we generated tetracistronic minigenomes encoding VP24 nuclear import and/or export signal mutants. The minigenomes, which also encode Renilla luciferase and viral proteins VP40 and GP, were used to generate transcription and replication competent virus-like particles (trVLPs) that can be used to assess EBOV RNA synthesis, gene expression, entry and viral particle production. With this system, we confirmed that NES or IMPA binding site mutations altered VP24 nuclear localization, demonstrating functional trafficking signals. While these mutations minimally affected transcription and replication, the trVLPs exhibited impaired infectivity and formation of shortened nucleocapsids for the IMPA binding mutant. For the NES mutants, infectivity was reduced approximately 1000-fold. The NES mutant could still suppress IFN signaling but failed to promote nucleocapsid formation. To determine whether VP24 nuclear export is required for infectivity, the residues surrounding the wildtype NES were mutated to alanine or the VP24 NES was replaced with the Protein Kinase A Inhibitor NES. While nuclear export remained intact for these mutants, infectivity was severely impaired. These data demonstrate that VP24 undergoes nuclear trafficking and illuminates a separate and critical role for the NES and surrounding sequences in infectivity and nucleocapsid assembly.

Dataset Information

Characteristics of exhaled particle production in healthy volunteers: possible implications for infectious disease transmission.

Publications

Characteristics of exhaled particle production in healthy volunteers: possible implications for infectious disease transmission.

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