Translational Aspects of the Human Respiratory Virome

Abstract

Despite the dominant role of community-acquired respiratory viruses as etiological agents of disease, there has been little focus to date on the translation of rapidly developing diagnostic modalities, such as next-generation sequencing techniques in the examination of lower respiratory tract samples. When applied, these techniques should inform strategies to both understand the nexus between health and disease states of the respiratory virome, and drive a paradigm shift in how the practicing pulmonologist views the conceptual framework of respiratory infections. The lower respiratory tract was once thought to be a sanctuary site from microbiological colonization owing to the efficacy of upper airway-protective mechanisms and the host mucosal barrier function of the lower airways, combined with both innate and adaptive immune responses. As a small number of recent studies confirm, this is a naive vision of the lung, the viral component of which parallels recent revelations from respiratory microbiome studies. Hence, it is now timely to revise our thinking regarding the constituents, diversity, and changing nature of the respiratory virome in health and disease. One area worthy of focus is the interface between community-acquired respiratory viruses and the respiratory virome to better understand the dynamics in acute infection, as well as the factors that may lead to viral persistence and chronic disease. Given recent advances in metagenomics, the tools are now at hand to accomplish these goals.

The role of acute and chronic respiratory colonization and infections in the pathogenesis of COPD

“…The respiratory tract contains genetic material from eukaryotic viruses such as anelloviruses, herpesviruses and papillomaviruses, as well as retroviruses that may establish persistent asymptomatic infections and bacteriophages, which dominate the virome. [142][143][144][145] In the lung, the virome is highly variable between individuals and is strongly influenced by environmental conditions such as oxygen availability. 144 Unfortunately, in many studies, a large proportion of sequencing reads are not matched to a reference genome and it is unclear whether the identified viruses are commensal or a latent infection.…”

Spatiotemporal Virus Surveillance for Severe Acute Respiratory Infections in Resource-limited Settings: How Deep Need We Go?

“…Following the discovery of molecular cloning, nucleic acid sequencing, and polymerase chain reaction, the wonderland of molecular biology has opened its doors again to virtually unlimited possibilities, as next-generation/deep sequencing or, better, massive parallel sequencing allows for the comprehensive analysis of all genomic nucleic acids of any origin in any given sample in real time. Initially applied to the bacterial microbiome, deep sequencing has similarly detected a multitude of viral genome sequences, and changed hitherto common views on persisting viral infections [1], putting forward the concept of the "virome" in general, and of the "human viromes" in particular [2]. While the numeric summary of viral genome sequences is mind-blowing, even after careful annotation and curation through refined bioinformatic tools, the utility of massive parallel sequencing has been prominently demonstrated in epidemiologic cluster analysis, for example, leading to the identification of a novel arenavirus as the cause of donor-derived death of 3 solid organ transplant recipients [3], or of a novel human polyomavirus causing lethal multiorgan failure in a pancreas transplant recipient [4].…”

Metagenomic Approaches to Assess Bacteriophages in Various Environmental Niches

“…Furthermore, the impact of diseases such as cystic fibrosis (CF) and human immunodeficiency virus (HIV) infection on the lung microbiome has recently received justified research scrutiny [140,141,142]. In contrast to the array of studies on the lung microbiome, relatively few studies have looked at the lung virome, although the value of such studies has recently been highlighted [143]. Therefore, it is likely that an increasing number of lung virome studies will be undertaken in the near future.…”