Viruses in cystic fibrosis patients’ airways

Abstract

Although bacteria have historically been considered to play a major role in cystic fibrosis (CF) airway damage, a strong impact of respiratory viral infections (RVI) is also now recognized. Emerging evidence confirms that respiratory viruses are associated with deterioration of pulmonary function and exacerbation and facilitation of bacterial colonization in CF patients. The aim of this review is to provide an overview of the current knowledge on respiratory viruses in CF airways, to discuss the resulting inflammation and RVI response, to determine how to detect the viruses, and to assess their clinical consequences, prevalence, and interactions with bacteria. The most predominant are Rhinoviruses (RVs), significantly associated with CF exacerbation. Molecular techniques, and especially multiplex PCR, help to diagnose viral infections, and the coming rise of metagenomics will extend knowledge of viral populations in the complex ecosystem of CF airways. Prophylaxis and vaccination are currently available only for Respiratory syncytial and Influenza virus (IV), but antiviral molecules are being tested to improve CF patients' care. All the points raised in this review highlight the importance of taking account of RVIs and their potential impact on the CF airway ecosystem.

Viral strategies predisposing to respiratory bacterial superinfections

“…However, impairments of macrophage and neutrophil antibacterial defense functions have been described in CF as a consequence of viral infections (Table 1). 34,91,92 AM play a fundamental role in CF lung pathology. When exposed to antiviral cytokines, such as IFN‐γ, undifferentiated macrophages polarize into M1 macrophages, these in turn: (a) demonstrate a hyperinflammatory phenotype; (b) are ineffective in resolving inflammation; (c) inadequately clear bacteria; and (d) secrete elevated amounts of reactive oxygen species and proinflammatory mediators 80,92 .…”

“…However, impairments of macrophage and neutrophil antibacterial defense functions have been described in CF as a consequence of viral infections (Table 1). 34,91,92 AM play a fundamental role in CF lung pathology.…”

“…80,92 Effective bacterial internalization of AM is further prevented by opsonin cleavage on their surface receptors by the free neutrophil elastase present in even higher concentrations in the CF airways during viral infections. 91,93 Moreover, AM intracellular bacterial killing is hampered by the alkalinization of the phagolysosome milieu by the abnormal bicarbonate and chloride transport related to the defective cystic fibrosis transmembrane conductance regulator (CFTR). 34 Moreover, the relative airway hypoxia, increased by viral infections, may trigger alterations of the microRNA content, leading to increased production of tumor necrosis factor-α (TNF-α) and IL-8.…”

Deciphering the Ecology of Cystic Fibrosis Bacterial Communities: Towards Systems-Level Integration

“…[18] in the airways of people with CF, although their involvement in respiratory disease remains controversial and largely understudied [10,19,20]. Metagenomic studies have also revealed an impact of respiratory viral infections in CF airway damage [21][22][23], as well as the presence of bacterial viruses (phages) in CF airways [24,25]. Phages may play roles in infection dynamics, perhaps by limiting specific bacterial populations and facilitating the adaptation of bacteria to CF airway conditions and/or the spread of antimicrobial resistance (e.g., through transduction) [26], as well as providing a potential therapeutic avenue.…”

“…Phages may play roles in infection dynamics, perhaps by limiting specific bacterial populations and facilitating the adaptation of bacteria to CF airway conditions and/or the spread of antimicrobial resistance (e.g., through transduction) [26], as well as providing a potential therapeutic avenue. However, due to the lack of universal gene markers for viruses (as opposed to bacterial 16S ribosomal RNA gene), the overwhelming majority of investigations of CF microbiota have focused on bacteria [22]. Consequently, we will mainly review studies on the bacterial fraction of the CF airway microbiome, beginning with an overview of the CF microbiota and the factors that potentially affect its community structure, composition, and diversity, then moving on to the important role of the functional interaction patterns in development of precision medicine tailored to the microbiome of individual people with CF.…”