Non-Coding RNAs and Their Role in Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (hMPV) Infections

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Abstract

Recent high-throughput sequencing revealed that only 2% of the transcribed human genome codes for proteins, while the majority of transcriptional products are non-coding RNAs (ncRNAs). Herein, we review the current knowledge regarding ncRNAs, both host- and virus-derived, and their role in respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) infections. RSV is known as the most common cause of lower respiratory tract infection (LRTI) in children, while hMPV is also a significant contributor to LRTI in the pediatrics population. Although RSV and hMPV are close members, belonging to the Pneumoviridae family, they induce distinct changes in the ncRNA profile. Several types of host ncRNAs, including long ncRNA (lncRNA), microRNAs (miRNAs), and transfer RNA (tRNA)-derived RNA fragments (tRFs), are involved as playing roles in RSV and/or hMPV infection. Given the importance of ncRNAs in regulating the expression and functions of genes and proteins, comprehensively understanding the roles of ncRNAs in RSV/hMPV infection could shed light upon the disease mechanisms of RSV and hMPV, potentially providing insights into the development of prevention strategies and antiviral therapy. The presence of viral-derived RNAs and the potential of using ncRNAs as diagnostic biomarkers are also discussed in this review.

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Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life.

Nele Sigurs, Fatma Aljassim, Bengt Kjellman … (2010)

An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma. Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge. Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO. Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.

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Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13.

Nele Sigurs, Per M Gustafsson, Ragnar Bjarnason … (2005)

We have prospectively studied wheezing disorder and allergy in 47 children hospitalized with respiratory syncytial virus (RSV) bronchiolitis in infancy and 93 matched control subjects. Subjects with at least three episodes of wheezing were defined as recurrent wheezers and as having asthma if the episodes were doctor verified. Here we report the outcome at age 13 years in 46/47 children with RSV and 92/93 control subjects. Wheezing disorder and clinical allergy were estimated using a questionnaire. Skin prick tests were performed and serum IgE antibodies measured. Spirometry was undertaken at rest, after dry air challenge, and after beta2-agonist inhalation. The occurrence of symptoms over the previous 12 months was significantly higher in the RSV group than among the control subjects, 43% versus 8% for asthma/recurrent wheezing and 39% versus 15% for allergic rhinoconjunctivitis. Sensitization to common inhaled allergens was more frequent in the RSV group than in the control subjects, judged by skin prick tests (50% versus 28%; p = 0.022), or by serum IgE antibodies (45% versus 26%; p = 0.038). Compared with the control subjects, the RSV group showed mild airway obstruction both at rest and after bronchodilation, and had slightly more reactive airways. RSV bronchiolitis in infancy severe enough to cause hospitalization is a risk factor for allergic asthma in early adolescence.

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Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells.

Vedashree Ramakrishnaiah, Christine Thumann, Isabel Fofana … (2013)

Recent evidence indicates there is a role for small membrane vesicles, including exosomes, as vehicles for intercellular communication. Exosomes secreted by most cell types can mediate transfer of proteins, mRNAs, and microRNAs, but their role in the transmission of infectious agents is less established. Recent studies have shown that hepatocyte-derived exosomes containing hepatitis C virus (HCV) RNA can activate innate immune cells, but the role of exosomes in the transmission of HCV between hepatocytes remains unknown. In this study, we investigated whether exosomes transfer HCV in the presence of neutralizing antibodies. Purified exosomes isolated from HCV-infected human hepatoma Huh7.5.1 cells were shown to contain full-length viral RNA, viral protein, and particles, as determined by RT-PCR, mass spectrometry, and transmission electron microscopy. Exosomes from HCV-infected cells were capable of transmitting infection to naive human hepatoma Huh7.5.1 cells and establishing a productive infection. Even with subgenomic replicons, lacking structural viral proteins, exosome-mediated transmission of HCV RNA was observed. Treatment with patient-derived IgGs showed a variable degree of neutralization of exosome-mediated infection compared with free virus. In conclusion, this study showed that hepatic exosomes can transmit productive HCV infection in vitro and are partially resistant to antibody neutralization. This discovery sheds light on neutralizing antibodies resistant to HCV transmission by exosomes as a potential immune evasion mechanism.

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Journal

Journal ID (nlm-ta): Viruses

Journal ID (iso-abbrev): Viruses

Journal ID (publisher-id): viruses

Title: Viruses

Publisher: MDPI

ISSN (Electronic): 1999-4915

Publication date (Electronic): 21 March 2020

Publication date Collection: March 2020

Volume: 12

Issue: 3

Electronic Location Identifier: 345

Affiliations

[1 ]Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555, USA; wenwu@ 123456utmb.edu (W.W.); euchoi@ 123456utmb.edu (E.-J.C.)

[2 ]miRcore, Ann Arbor, MI 48105, USA; inhanlee99@ 123456gmail.com

[3 ]Department of Cancer System Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang-si Gyeonggi-do 10408, Korea; yslee@ 123456ncc.re.kr

[4 ]Sealy Center for Molecular Medicine, The University of Texas Medical Branch, Galveston, TX 77555, USA

[5 ]The Institute of Translational Sciences, The University of Texas Medical Branch, Galveston, TX 77555, USA

[6 ]The Institute for Human Infections and Immunity, The University of Texas Medical Branch, Galveston, TX 77555, USA

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[* ]Correspondence: xibao@ 123456utmb.edu ; Tel.: +409-772-1777

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Yong Sun Lee https://orcid.org/0000-0001-9689-3410

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Publisher ID: viruses-12-00345

DOI: 10.3390/v12030345

PMC ID: 7150941

PubMed ID: 32245206

SO-VID: 842418fa-eadf-4f83-8c2d-8c579ddbedec

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Non-Coding RNAs and Their Role in Respiratory Syncytial Virus (RSV) and Human Metapneumovirus (hMPV) Infections

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European Respiratory Society: COVID-19

Most cited references 77

Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life.

Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13.

Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells.

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