Lower Airway Virology in Health and Disease—From Invaders to Symbionts

Abstract

Studies of human airway virome are relatively recent and still very limited. Culture-independent microbial techniques showed growing evidence of numerous viral communities in the respiratory microbial ecosystem. The significance of different acute respiratory viruses is already known in the pathogenesis of chronic conditions, such as asthma, cystic fibrosis (CF), or chronic obstructive lung disease (COPD), and their exacerbations. Viral pathogens, such as influenza, metapneumovirus, parainfluenza, respiratory syncytial virus, or rhinovirus, have been associated with impaired immune response, acute exacerbations, and decrease in lung function in chronic lung diseases. However, more data have attributed a role to Herpes family viruses or the newly identified Anelloviridae family of viruses in chronic diseases, such as asthma, idiopathic pulmonary fibrosis (IPF), or CF. Impaired antiviral immunity, bacterial colonization, or used medication, such as glucocorticoids or antibiotics, contribute to the imbalance of airway microbiome and may shape the local viral ecosystem. A specific part of virome, bacteriophages, frames lung microbial communities through direct contact with its host, the specific bacteria known as Pseudomonas aeruginosa or their biofilm formation. Moreover, antibiotic resistance is induced through phages via horizontal transfer and leads to more severe exacerbations of chronic airway conditions. Morbidity and mortality of asthma, COPD, CF, and IPF remains high, despite an increased understanding and knowledge about the impact of respiratory virome in the pathogenesis of these conditions. Thus, more studies focus on new prophylactic methods or therapeutic agents directed toward viral–host interaction, microbial metabolic function, or lung microbial composition rearrangement.

Lung Microbiome Participation in Local Immune Response Regulation in Respiratory Diseases

“…In healthy subjects, the similarity of the lung and mouth microbiota varies considerably; it is undetermined whether this variation is persistent over time within subjects or is correlated with clinical phenomena such as esophageal reflux, laryngeal dysfunction, and oral hygiene [6,7]. Metagenomics techniques have demonstrated that in healthy subjects, microorganisms include viruses (virome) [8], fungi (mycome), and bacteria (bacteriome) have an important role in homeostasis [9]. These also participate in host protection against pathogenic microorganisms [10].…”

The Microbiome in Cystic Fibrosis Pulmonary Disease

“…Virome: The CF lung virome is strongly affected by the mucosal environment and impaired immunity [35]. Common respiratory viruses are found in 60% of CF patients (more than in the general population) and cause greater morbidity than in non-CF subjects [80]. Presence correlates with inflammation, as they interfere with IFN and NF-kappaB pathways, and with bacterial co-infection (including P. aeruginosa), inducing exacerbation and impaired lung function [35,80].…”

“…Common respiratory viruses are found in 60% of CF patients (more than in the general population) and cause greater morbidity than in non-CF subjects [80]. Presence correlates with inflammation, as they interfere with IFN and NF-kappaB pathways, and with bacterial co-infection (including P. aeruginosa), inducing exacerbation and impaired lung function [35,80]. In addition to eukaryotic viruses, the CF lung microbiome contains phages adapted to this particular environment [35,72,81], and known to impact the microbiome, driving pathogen adaptation and antibiotic resistance [81].…”

Time to Say Goodbye to Bronchiolitis, Viral Wheeze, Reactive Airways Disease, Wheeze Bronchitis and All That

“…Our understanding of the role that the respiratory microbiome (which varies across the varying niches from nose to distal airway) and that of the gut in promoting health and disease within the airways is still at a relatively early stage (105)(106)(107). What seems clear is that our relatively simplistic views of a single organism causing a given acute illness, which is largely based on Kock's postulates formulated more than 120 years ago (108), grossly oversimplifies the complex interactions of individual microorganisms with other members of the microbiome and the host.…”