Respiratory syncytial virus modifies microRNAs regulating host genes that affect virus replication.
Respiratory syncytial virus (RSV) causes substantial morbidity and life-threatening lower respiratory tract disease in infants, young children and the elderly. Understanding the host response to RSV infection is critical for developing disease-intervention approaches. The role of microRNAs (miRNAs) in post-transcriptional regulation of host genes responding to RSV infection is not well understood. In this study, it was shown that RSV infection of a human alveolar epithelial cell line (A549) induced five miRNAs (let-7f, miR-24, miR-337-3p, miR-26b and miR-520a-5p) and repressed two miRNAs (miR-198 and miR-595), and showed that RSV G protein triggered let-7f expression. Luciferase-untranslated region reporters and miRNA mimics and inhibitors validated the predicted targets, which included cell-cycle genes (CCND1, DYRK2 and ELF4), a chemokine gene (CCL7) and the suppressor of cytokine signalling 3 gene (SOCS3). Modulating let-7 family miRNA levels with miRNA mimics and inhibitors affected RSV replication, indicating that RSV modulates host miRNA expression to affect the outcome of the antiviral host response, and this was mediated in part through RSV G protein expression.
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Abhijeet
A
Bakre
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Patricia
P
Mitchell
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Jonathan K
JK
Coleman
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Les P
LP
Jones
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Geraldine
G
Saavedra
Division of Allergy and Immunology, Department of Internal Medicine, USF Health, Tampa, FL 33612, USA.
Michael
M
Teng
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
S Mark
SM
Tompkins
Department of Infectious Diseases, University of Georgia, Athens, GA 30602, USA.
Ralph A
RA
Tripp
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*
D035683:MicroRNAs